To assess the image quality and effective radiation dose of prospectively electrocardiogram (ECG)-gated high-pitch spiral acquisition mode (flash mode) of dual-source CT (DSCT) coronary angiography (CTCA) in patients with high heart rates (HRs) as compared with retrospectively ECG-gated spiral acquisition mode.
Materials and Methods
Two hundred and sixty-eight consecutive patients (132 female, mean age: 55 ± 11 years) with mean HR > 65 beats per minute (bpm) were prospectively included in this study. The patients were divided into two groups. Collection was performed in group A CTCA using flash mode setting at 20-30% of the R-R interval, and retrospectively ECG-gated spiral acquisition mode in group B. The image noise, contrast-to-noise ratio (CNR), image quality scores, effective radiation dose and influencing factors on image quality between the two groups were assessed.
There were no significant differences in image quality scores and proportions of non-diagnostic coronary artery segments between two groups (image quality scores: 1.064 ± 0.306 [group A] vs. 1.084 ± 0.327 [group B], p = 0.063; proportion of non-diagnostic coronary artery segments: segment-based analysis 1.52% (group A) vs. 1.74% (group B), p = 0.345; patient-based analysis 7.5% (group A) vs. 6.7% (group B), p = 0.812). The estimated radiation dose was 1.0 ± 0.16 mSv in group A and 7.1 ± 1.05 mSv in group B (p = 0.001).
In conclusion, in patients with HRs > 65 bpm without cardiac arrhythmia, the prospectively high-pitch spiral-acquisition mode with image-acquired timing set at 20-30% of the R-R interval provides a similar image quality and low rate of non-diagnostic coronary segments to the retrospectively ECG-gated low-pitch spiral acquisition mode, with significant reduction of radiation exposure.
High-pitch dual-source CT; Prospectively ECG-gated; Coronary angiography; High heart rates
Surface structures and surface interactions are key factors that influence the reactivity and stability of nanomaterials. Combining experimental and theoretical investigations, we illustrate the roles of surface interactions in the formation and phase stability of an unusual TiO2(B) polymorph that preferentially exposes the plane of the highest surface energy. We find that the favorable bidentate adsorption of ethylene glycol on the TiO2(B)(010) plane enables the formation and confines the phase stability of TiO2(B) ultrathin nanosheets. The essence of such selective generation of the unusual nanostructure with ultrahigh purity both in phase and morphology lies in the specific adsorption driven by the matched interface structures. The general roles of structural match for the activity and stability in physical interactions are elucidated.
Laccase-2 is a highly conserved multicopper oxidase that functions in insect cuticle pigmentation and tanning. In many species, alternative splicing gives rise to two laccase-2 isoforms. A comparison of laccase-2 sequences from three orders of insects revealed eleven positions at which there are conserved differences between the A and B isoforms. Homology modeling suggested that these eleven residues are not part of the substrate binding pocket. To determine whether the isoforms have different kinetic properties, we compared the activity of laccase-2 isoforms from Tribolium castaneum and Anopheles gambiae. We partially purified the four laccases as recombinant enzymes and analyzed their ability to oxidize a range of laccase substrates. The predicted endogenous substrates tested were dopamine, N-acetyldopamine (NADA), N-β-alanyldopamine (NBAD) and dopa, which were detected in T. castaneum previously and in A. gambiae as part of this study. Two additional diphenols (catechol and hydroquinone) and one non-phenolic substrate (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) were also tested. We observed no major differences in substrate specificity between the A and B isoforms. Dopamine, NADA and NBAD were oxidized with catalytic efficiencies ranging from 51 – 550 min−1 mM−1. These results support the hypothesis that dopamine, NADA and NBAD are endogenous substrates for both isoforms of laccase-2. Catalytic efficiencies associated with dopa oxidation were low, ranging from 8 – 30 min−1 mM−1; in comparison, insect tyrosinase oxidized dopa with a catalytic efficiency of 201 min−1 mM−1. We found that dopa had the highest redox potential of the four endogenous substrates, and this property of dopa may explain its poor oxidation by laccase-2. We conclude that laccase-2 splice isoforms are likely to oxidize the same substrates in vivo, and additional experiments will be required to discover any isoform-specific functions.
multicopper oxidase; laccase; substrate; insect; cuticle
Laccases are copper-containing oxidases that are involved in sclerotization of the cuticle of mosquitoes and other insects. Oxidation of exogenous compounds by insect laccases may have the potential to produce reactive species toxic to insects. We investigated two classes of substituted phenolic compounds, halogenated di- and trihydroxybenzenes and substituted di-tert-butylphenols, on redox potential, oxidation by laccase and effects on mosquito larval growth. An inverse correlation between the oxidation potentials and laccase activity of halogenated hydroxybenzenes was found. Substituted di-tert-butylphenols however were found to impact mosquito larval growth and survival. In particular, 2,4-di-tert-butyl-6-(3-methyl-2-butenyl)phenol (15) caused greater than 98% mortality of Anopheles gambiae larvae in a concentration of 180 nM, whereas 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-methylpropanal oxime (13) and 6,8-di-tert-butyl-2,2-dimethyl-3,4-dihydro-2H-chromene (33) caused 93% and 92% mortalities in concentrations of 3.4 and 3.7 μM, respectively. Larvae treated with di-tert-butylphenolic compounds died just before pupation.
Anopheles gambiae; anti-larval activity; halogenated di- and trihydroxybenzenes; laccases; mosquito larvicides; redox potential; substituted di-tert-butylphenols
Synthesized by glycogen synthase and starch synthases (SS) using ADP-glucose as the sugar donor molecule, glycogen and starch accumulate as predominant storage carbohydrates in most bacteria and plants, respectively. We have recently shown that the so-called “starch-less” Arabidopsis thaliana adg1–1 and aps1 mutants impaired in ADP-glucose pyrophosphorylase do indeed accumulate low starch content in normal growth conditions, and relatively high starch content when plants were cultured in the presence of microbial volatiles. Our results were strongly supported by data obtained using a highly sensitive method for confocal fluorescence microscopic visualization of iodine stained starch granules. Using Arabidopsis leaves from WT plants, aps1 plants, ss3/ss4 plants lacking both class III and class IV SS, gbss plants lacking the granule-bound SS, and sus1/sus2/sus3/sus4 plants lacking four genes that code for proteins with sucrose synthase activity, in this work we precisely describe the method for preparation of plant samples for starch microscopic examination. Furthermore, we show that this method can be used to visualize glycogen in bacteria, and pure starch granules, amylose and amylopectin.
Arabidopsis thaliana; adg1-1 mutant; aps1 mutant; ss3/ss4 mutant; concofal microscopy; glycogen; iodine staining; starch; sus1/sus2/sus3/sus4 mutant
Calcium phosphate (CaP) nanoparticles(NP) with an asymmetric lipid bilayer coating have been designed for targeted delivery of siRNA to the tumor. An anionic lipid, dioleoylphosphatydic acid (DOPA), was employed as the inner leaflet lipid to coat the nano-size CaP cores, which entrap the siRNA, such that the coated cores were soluble in organic solvent. A suitable neutral or cationic lipid was used as the outer leaflet lipid to form an asymmetric lipid bilayer structure verified by the measurement of NP zeta potential. The resulting NP was named LCP-II with a size of about 25 to 30 nm in diameter and contained a hollow core as revealed by TEM imaging. PEGylation of NP was done by including a PEG-phospholipid conjugate, with or without a targeting ligand anisamide, in the outer leaflet lipid mixture. The sub-cellular distribution studied in the sigma receptor positive human H460 lung cancer cells indicated that LCP-II could release more cargo to the cytoplasm than our previous lipid/protamine/DNA (LPD) formulation, leading to a significant (~40 fold in vitro and ~4 fold in vivo) improvement in siRNA delivery. Bio-distribution study showed that LCP-II required more PEGylation for MPS evasion than the previous LPD, probably due to increased surface curvature in LCP-II.
Asymmetric lipid bilayer; Calcium phosphate; Nanoparticle; siRNA delivery
Abscisic acid (ABA) is an essential hormone for plants to survive environmental stresses. At the center of the ABA signaling network is a subfamily of type 2C protein phosphatases (PP2Cs), which form exclusive interactions with ABA receptors and subfamily 2 Snfl-related kinase (SnRK2s). Here, we report a SnRK2-PP2C complex structure, which reveals marked similarity in PP2C recognition by SnRK2 and ABA receptors. In the complex, the kinase activation loop docks into the active site of PP2C, while the conserved ABA-sensing tryptophan of PP2C inserts into the kinase catalytic cleft, thus mimicking receptor-PP2C interactions. These structural results provide a simple mechanism that directly couples ABA binding to SnRK2 kinase activation and highlight a new paradigm of kinase-phosphatase regulation through mutual packing of their catalytic sites.
Pulsus paradoxus is an exaggeration of the normal inspiratory decrease in systolic blood pressure. Despite a century of attempts to explain this sign consensus is still lacking. To solve the controversy and reveal the exact mechanism, we reexamined the characteristic anatomic arrangement of the circulation system in the chest and designed these mechanical models based on related hydromechanic principles. Model 1 was designed to observe the primary influence of respiratory intrathoracic pressure change (RIPC) on systemic and pulmonary venous return systems (SVR and PVR) respectively. Model 2, as an equivalent mechanical model of septal swing, was to study the secondary influence of RIPC on the motion of the interventriclar septum (IVS), which might be the direct cause for pulsus paradoxus. Model 1 demonstrated that the simulated RIPC had different influence on the simulated SVR and PVR. It increased the volume of the simulated right ventricle (SRV) when the internal pressure was kept constant (8.16 cmH2O), while it had the opposite effect on PVR. Model 2 revealed the three major factors determining the respiratory displacement of IVS in normal and different pathophysiological conditions: the magnitude of RIPC, the pressure difference between the two ventricles and the intrapericardial pressure. Our models demonstrate that the different anatomical arrangement of the two venous return systems leads to a different effect of RIPC on right and left ventricles, and thus a pressure gradient across IVS that tends to shift IVS left- and rightwards. When the leftward displacement of IVS reaches a considerable amplitude in some pathologic condition such as cardiac tamponade, the pulsus paradoxus occurs.
The q arm of chromosome 1 is frequently amplified at the gene level in breast cancer. Since the significance of this is unclear we investigated whether 1q genes are overexpressed in this disease. The cDNA levels of 1q-located genes were analysed in a search for overexpressed genes. 26 genes mapping to the 1q arm show highly significant (P≤0.01) overexpression of transcripts in breast cancer compared to normal breast tissue. Amongst those showing the highest levels of overexpression in both expressed sequence tag (EST) and serial analysis of gene expression (SAGE) databases was enzyme quiescin Q6 sulfhydryl oxidase 1 (QSOX1). We investigated QSOX1 cDNA derived from T47D breast carcinoma cells by RT-PCR and 3′-RACE PCR and identified a novel extended form of QSOX1 transcript, containing a long 3′UTR, nearly double the size of the previously reported QSOX1 cDNA, and confirmed its 3′ end nucleotide sequence using RACE-PCR. We also used quantitative real-time PCR to analyse a panel of cDNAs derived from 50 clinically-graded normal and malignant breast tissue samples for the expression of QSOX1 mRNAs. QSOX1 transcription was elevated in an increasing proportion in the grade 2 and grade 3 tumours (graded according to the Nottingham prognostic index), with 10 of the 15 grade 3 tumours (67%) examined exceeding the normal range. There was a significant correlation between relative transcript level and clinical grade (P≤0.01) for all qPCR primer sets tested. QSOX1 mRNA levels, based on SAGE expression data, did not correlate with either Estrogen Receptor (ER) or Epidermal Growth Factor Receptor 2 (ErbB-2 or HER2/neu) expression. Our data indicate that QSOX1 is a potential new prognostic marker which may prove of use in the staging of breast tumours and the stratification of breast cancer patients.
Genetic polymorphisms of IRF5 are associated with an increased risk of lupus in humans. Here, we examined the role of IRF5 in the pathogenesis of pristane-induced lupus in mice. The pathological response to pristane in IRF5−/− mice shared many features with IFN-I receptor (IFNAR) −/− and TLR7−/− mice: production of anti-Sm/RNP autoantibodies, glomerulonephritis, generation of Ly6Chi monocytes, and IFN-I production all were greatly attenuated. Lymphocyte activation following pristane injection was greatly diminished in IRF5−/− mice and helper T cell differentiation was deviated from TH1 in wild type mice toward TH2 in IRF5−/− mice. TH cell development was skewed similarly in TLR7−/− or IFNAR−/− mice, suggesting that IRF5 alters T cell activation and differentiation by affecting cytokine production. Indeed, production of IFN-I, IL-12, and IL-23 in response to pristane was markedly decreased, whereas IL-4 increased. Unexpectedly, plasmacytoid dendritic cells (pDC) were not recruited to the site of inflammation in IRF5−/− or MyD88−/− mice, but were recruited normally in IFNAR−/− and TLR7−/− mice. In striking contrast to wild type mice, pristane did not stimulate local expression of CCL19 and CCL21 in IRF5−/− mice, suggesting that IRF5 regulates chemokine-mediated pDC migration independently of its effects on IFN-I. Collectively, these data indicate that altered production of IFN-I and other cytokines in IRF5−/− mice prevents pristane from inducing lupus pathology by broadly affecting T and B lymphocyte activation/differentiation. Additionally, we uncovered a new, IFN-I independent, role of IRF5 in regulating chemokines involved in the homing of pDCs and certain lymphocyte subsets.
Although anaplasmosis cases have been nationally identified in China, no human isolates of A. phagocytophilum have been obtained, which limits the analysis of any molecular and genetic contributions to patients' severe clinical manifestations and the study of the bacteria's pathogeneses in China. Given this situation, a joint project was conducted in 2009–2010. A total of 421 febrile cases of unknown etiology were collected and the patients' blood samples were collected for laboratory diagnoses including serologic diagnosis based on the four-fold rise in the anti- A. phagocytophilum IgG titer by indirect micro-immunofluorescence assay (IFA), positive PCR assay and confirmation of A. phagocytophilum DNA and positive culture of A. phagocytophilum and confirmed by amplification and sequencing of the 16S rRNA and ank A genes of the A. phagocytophilum isolates. A total of 570 ticks were collected from the patients' domestic animals (456) and from wild fields (114) for culturing and amplifying and sequencing the 16S rRNA gene of A. phagocytophilum. Phylogenetic analyses were performed on the 16S rRNA and ank A gene sequences of the isolates and the ticks tested in the study. A total of 46 (10.9%) confirmed and 16 (3.8%) probable cases were diagnosed and severe clinical features and higher mortality rates were observed in these Chinese patients. Five isolates were obtained and the 16S rRNA genes of the 5 isolates were conserved but variety for ank A genes. Two human isolates and 1 tick isolate from Shandong Peninsula, where all patients exhibited severe clinical manifestations, were grouped as one clan based on the phylogenetic analyses, while 2 other human isolates were clustered in a second clan. 43.5% of H. longicornis were infected with A. phagocytophilum.The present study is the first to obtain clinical isolates of A. phagocytophilum in China. The diversity of the ank A genes of Chinese isolates will help us to further discern the relationship between the variations in the ank A genes and the severity of the disease's clinical manifestations in China.
To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes after cataract extraction.
Twenty New Zealand white rabbits accepted cataract extraction plus intraocular lens implantation and their left eyes were intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid (PLGA) as a carrier and their right eyes were injected with empty MS. The changes in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA concentration in aqueous humor were examined postoperatively and all the eyes were enucleated 3 months after surgery for histopathological and morphological examination with light microscopy and electron microscopy.
Conjunctival hyperemia, corneal edema, intraocular pressure and anterior chamber response of experimental and control eyes were similar, while PCO in CsA-MS injected eyes was greatly improved compared with that in control eyes. Posterior capsules in CsA-MS injected eyes were smooth and lens epithelial cells (LEC) did not proliferate significantly (P>0.05), while LEC in posterior capsule of control eyes had different degrees of proliferation and cortical regeneration. LEC in CsA-MS injected eyes were not functionally active and underwent apoptosis, whereas LEC in control eyes were functionally active (F-test, P=0.025). In addition, the corneal ultrastructure showed no differences between CsA-MS and MS injected eyes.
CsA-MS has high bioavailability in rabbit eyes and could inhibit postoperative PCO occurrence and development during the study period, suggesting that CsA-MS may be a promising, effective and safe administration route to prevent PCO in clinic.
sustained cyclosporine A delivery microsphere; posterior capsular opacification; rabbit eyes
Protein pathways are dynamic and highly coordinated spatially and temporally, capable of performing a diverse range of complex chemistries and enzymatic reactions with precision and at high efficiency. Biotechnology aims to harvest these natural systems to construct more advanced in vitro reactions, capable of new chemistries and operating at high yield. Here, we present an efficient Multiplex Automated Genome Engineering (MAGE) strategy to simultaneously modify and co-purify large protein complexes and pathways from the model organism Escherichia coli to reconstitute functional synthetic proteomes in vitro. By application of over 110 MAGE cycles, we successfully inserted hexa-histidine sequences into 38 essential genes in vivo that encode for the entire translation machinery. Streamlined co-purification and reconstitution of the translation protein complex enabled protein synthesis in vitro. Our approach can be applied to a growing area of applications in in vitro one-pot multi-enzyme catalysis (MEC) to manipulate or enhance in vitro pathways such as natural product or carbohydrate biosynthesis.
Genome engineering; MAGE; cell-free protein synthesis; multi-enzyme catalysis; protein purification
Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved energy sensor sensitive to changes in cellular AMP/ATP ratio which is activated by phosphorylation (pAMPK). pAMPK levels decrease in peripheral tissues with age, but whether this also occurs in the aged brain, and how this contributes to the ability of the aged brain to cope with ischemic stress is unknown. This study investigated the activation of AMPK and the response to AMPK inhibition after induced stroke in both young and aged male mice. Baseline levels of phosphorylated AMPK were higher in aged brains compared to young mice. Stroke-induced a robust activation of AMPK in young mice, yet this response was muted in the aged brain. Young mice had larger infarct volumes compared with aged animals; however, more severe behavioral deficits and higher mortality were seen in aged mice after stroke. Inhibition of AMPK with Compound C decreased infarct size in young animals, but had no effect in aged mice. Compound C administration led to a reduction in brain ATP levels and induced hypothermia, which led to enhanced neuroprotection in young but not aged mice. This work demonstrates that aging increases baseline brain pAMPK levels; aged mice have a muted stroke-induced pAMPK response; and that AMPK inhibition and hypothermia are less efficacious neuroprotective agents in the aged brain. This has important translational relevance for the development of neuroprotective agents in preclinical models and our understanding of the enhanced metabolic stress experienced by the aged brain.
Aging; AMPK; Compound C; Hypothermia; Ischemic stroke; Middle cerebral artery occlusion (MCAO)
CACNA1C gene polymorphism (rs1006737) is a susceptibility factor for both schizophrenia (SCZ) and bipolar disorder (BP). However, its role in working memory, a cognitive function that is impaired in both diseases, is not clear. Using three samples, including healthy controls, patients with SCZ, and patients currently in manic episodes of BP, this study tested the association between the SNP rs1006737 and spatial working memory as measured by an N-back task and a dot pattern expectancy (DPX) task. Among SCZ patients and healthy controls, the clinical risk allele was associated with impaired working memory, but the association was either in opposite direction or non-significant in patients with BP. These results indicated that rs1006737 may have differential effects on working memory in different disease populations and pointed to the necessity for more studies in different patient populations.
schizophrenia; CACNA1C; working memory; polymorphism; Author keywords:biological psychiatry; cognition; depression; unipolar/bipolar; schizophrenia/antipsychotics; molecular genetics; working memory
We examined the effect of three clinically used antimicrobials on Streptococcus mutans UA159 biofilm detachment under flow conditions. Sodium fluoride (NaF) and chlorhexidine at MIC levels promoted biofilm detachment and inhibited detachment when concentrations were higher than the MIC and reduced detached-cell viability only at high concentrations. Ampicillin at all concentrations tested inhibited detachment and reduced the percentage of viable biofilm-detached cells. All the three antimicrobial treatments reduced biofilm live/dead cell ratios.
This paper reports capture and detection of pathogenic bacteria based on AC dielectrophoresis (DEP) and electrochemical impedance spectroscopy (EIS) employing an embedded vertically aligned carbon nanofiber (VACNF) nanoelectrode array (NEA) vs. a macroscopic indium tin oxide (ITO) transparent electrode in “points-and-lid” configuration. The nano-DEP device was fabricated using photolithography processes to define an exposed active region on a randomly distributed NEA and a microfluidic channel on ITO to guide the flow of labeled E. coli cells, respectively, and then bond them into a fluidic chip. A high frequency (100 kHz) AC field was applied to generate positive DEP at the tips of exposed CNFs. Enhanced electric field gradient was achieved due to reduction in electrode size down to nanometer scale which helped to overcome the large hydrodynamic drag force experienced by E. coli cells at high flow velocities (up to 1.6 mm/sec). This DEP device was able to effectively capture a significant number of E. coli. Significant decrease in the absolute impedance (|Z|) at the NEA was observed by EIS experiments. The results obtained in this study suggest the possibility of integration of a fully functional electronic device for rapid, reversible and label-free capture and detection of pathogenic bacteria.
Bacterial Capture; Dielectrophoresis; Dielectrophoretic Impedance Measurement; Nanoelectrode Array; Vertically Aligned Carbon Nanofibers
The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) isolates have showed accelerating evolution under the great immune pressure in China in recent years. Here, we report the complete genome sequence of the HP-PRRSV variant GX1001 isolated from a vaccinated backyard piglet.
Regulatory T cells (Treg) expressing the transcription factor forkhead-box protein P3 (Foxp3) have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC) the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC).
Methods and Findings
Gene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival.
Our findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression.
The GX1002 strain is a highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) characterized by a continuous 2-nucleotide deletion at positions 119 and 120 in the 5′ untranslated region. This differs from prevalent HP-PRRSVs in China, which have a deletion of only 1 nucleotide at position 119. Here we report the complete genome sequence of the GX1002 strain.
Thromboxane synthase (TXAS) and thromboxane A2 receptor (TP), two critical components for thromboxane A2 (TXA2) signaling, have been suggested to be involved in cancer invasion and metastasis. However, the mechanisms by which TXA2 promotes these processes are still unclear. Here we show that TXA2 mimetic, I-BOP, induced monocyte chemoattractant protein -1(MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) expression at both mRNA and protein levels in human lung adenocarcinoma A549 cells stably over-expressing TP receptor α isoform (A549-TPα). The induction of MCP-1 was also found in other lung cancer cells H157 and H460 that express relatively high levels of endogenous TP. Using specific inhibitors of several signaling molecules and promoter/luciferase assay, we identified that transcription factor SP1 mediates I-BOP-induced MCP-1 expression. Furthermore, supernatants from I-BOP-treated A549-TPα cells enhanced MCP-1-dependent migration of RAW 264.7 macrophages. Moreover, co-culture of A549 cells with RAW 264.7 macrophages induced expression of MMPs, VEGF and MCP-1 genes, and increased the invasive potential in A549 cells. These findings suggest that TXA2 may stimulate invasion of cancer cells through MCP-1-mediated macrophage recruitment.
Melatonin is involved in the regulation of circadian and seasonal rhythms and immune function. Prior research reported low melatonin levels in autism spectrum disorders (ASD). ASMT located in pseudo-autosomal region 1 encodes the last enzyme of the melatonin biosynthesis pathway. A previous study reported an association between ASD and single nucleotide polymorphisms (SNPs) rs4446909 and rs5989681 located in the promoter of ASMT. Furthermore, rare deleterious mutations were identified in a subset of patients. To investigate the association between ASMT and autism, we sequenced all ASMT exons and its neighboring region in 398 Chinese Han individuals with autism and 437 healthy controls. Although our study did not detect significant differences of genotypic distribution and allele frequencies of the common SNPs in ASMT between patients with autism and healthy controls, we identified new rare coding mutations of ASMT. Among these rare variants, 4 were exclusively detected in patients with autism including a stop mutation (p.R115W, p.V166I, p.V179G, and p.W257X). These four coding variants were observed in 6 of 398 (1.51%) patients with autism and none in 437 controls (Chi-Square test, Continuity Correction p = 0.032, two-sided). Functional prediction of impact of amino acid showed that p.R115W might affect protein function. These results indicate that ASMT might be a susceptibility gene for autism. Further studies in larger samples are needed to better understand the degree of variation in this gene as well as to understand the biochemical and clinical impacts of ASMT/melatonin deficiency.
The aim of this study was to evaluate the management of acute adult diarrhea in China and assess adherence of clinical practice to national guidelines and 2012 World Gastroenterology Organization guidelines.
A cross-sectional survey was carried out among physicians in 20 hospitals in two different areas of China (Beijing, 10; Shaanxi province, 10). Summary statistics were calculated for the overall study group and for each region. Between-region differences were assessed with χ2 or t-tests.
Data were collected for 800 patients (≥18 years; mean ± SD age 37.0 ± 16.3 years; 56.4% female). The mean ± SD time between diarrhea onset and visiting a diarrhea clinic was 2.4 ± 1.6 days; this interval was significantly shorter in Beijing than Shaanxi (2.0 ± 1.4 vs 2.8 ± 1.8 days, respectively; p < 0.001). Overall, 31.4% of patients self-medicated before visiting the clinic, most commonly with antibiotics. Routine stool examinations were ordered for 70.6% of patients, vibrio cholera stool culture for 57.5%, but non-vibrio bacteria stool culture for only 11.4%. Only 61.6% of patients received fluid and electrolyte therapy: 28.3% oral rehydration solution (ORS) and 33.4% intravenous fluids (even though only 13.8% needed). Antibiotics were the most common drugs (60.8%) and the most common antibiotics were fluoroquinolones, followed by aminoglycosides. Totally 51.3% of patients received irrational antibiotic treatment (unnecessary for 47.9%; indicated but not prescribed for 3.4%). After antibiotics, the most commonly prescribed drugs were dioctahedral smectite (59.3%); For Shaanxi compared with Beijing, less individuals received ORS (7.8% vs 48.5%,respectively; p < 0.001) and more received intravenous fluids (46.3% vs 20.5%, respectively; p < 0.001). Significantly more of the patients in Shaanxi province were administered antibiotics (64.5% vs 57%, respectively; p = 0.03), and more received intravenous antibiotics than Beijing (49.0% vs 27.0%, respectively; p < 0.001).
Adherence to both national guidelines and 2012 World Gastroenterology Organization guidelines for the management of acute diarrhea in adult was limited among tertiary hospital physicians. The findings suggest nationwide education and effective health policies are needed to improve medical practice and reduce the unnecessary burden on the healthcare system.
Acute diarrhea; Adults; Cross-sectional survey; China
The purpose of this study is to investigate whether the dynamic hip immobilization is more favourable for lessening ischemic injury to the immature femoral head than a static immobilization. 152 Japanese white rabbits were divided into four groups randomly, and the hips were immobilized into “human” position (group A), “frog leg” position (group B) and “dynamic frog leg” position (group C). Group D was used as control. Ten rabbits in each group were killed, and the hip specimens were harvested at 1, 2, and 3 weeks after immobilization. Bcl-2/Bax expression balance and chondrocytes apoptosis were analyzed. The remaining eight rabbits in each group were used to measure the blood supply of capital femoral epiphysis by selective vascular perfusion with Indian ink. The Bcl-2/Bax expression ratio in group C was significantly increased than that in group A and B (p<0.001), while that was not significantly different from control group (p=0.0592). At three weeks after immobilization, the average apoptotic ratio was 36.7%, 45.8%, and 26.7% in group A, B and C, respectively (p<0.01). There was no significant difference between group C and normal control (p=0.0597). The perfusion ratio was 0.03±0.03, 0.03±0.02, and 0.08±0.03 in group A, B and C respectively, and 0.12±0.04 in control group (p<0.05). Thus, the dynamic immobilization model exhibited a relatively less chondrocytes apoptosis and disturbance to the femoral head perfusion than other immobilizations in vivo, which therefore may be useful for reducing avascular necrosis following the treatment of developmental dysplasia of the hip.
Dynamic immobilization; femoral head; blood supply; apoptosis
The purpose of this study was to assess the effects of berberine (BBR) on thermoregulation in mice exposed to hot (40°C) and cold (4°C) environmental conditions. Four groups of mice were assembled with three different dosages of BBR (0.2, 0.4, and 0.8 mg/kg) and normal saline (control). In room temperature, our largest dosage of BBR (0.8 mg/kg) can reduce rectal temperatures (Tc) of normal mice. In hot conditions, BBR can antagonize the increasing core body temperature and inhibit the expression of HSP70 and TNFα in mice; conversely, in cold conditions, BBR can antagonize the decreasing core body temperature and enhance the expression of TRPM8. This study demonstrates the dual ability of BBR in maintaining thermal balance, which is of great relevance to the regulation of HSP70, TNFα and TRPM8.