What is distinct about infants' "colic" cries?
To investigate (1) whether colic cries are acoustically distinct from pre-feed "hunger" cries; (2) the role of the acoustic properties of these cries versus their other properties in accounting for parents' concerns about colic. From a community sample, infants were selected who met Wessel colic criteria for amounts of crying and whose mothers identified colic bouts. Using acoustic analyses, the most intense segments of nine colic bouts were compared with matched segments from pre-feed cries presumed to reflect hunger. The colic cries did not have a higher pitch or proportion of dysphonation than the pre-feed cries. They did contain more frequent shorter utterances, but these resembled normal cries investigated in other studies. There is no evidence that colic cries have distinct acoustic features that are reproducible across samples and studies, which identify a discrete clinical condition, and which are identified accurately by parents. The most reliable finding is that colic cries convey diffuse acoustic and audible information that a baby is highly aroused or distressed. Non-acoustic features, including the prolonged, hard to soothe, and unexplained nature of the cries may be specific to colic cries and more important for parents. These properties might reflect temperament-like dispositions.


[Clinical efficacy of tolterodine for patients with overactive bladder after insufficient efficacy by monotherapy with alpha1-adrenoceptor antagonist].
The efficacy of alpha1-adrenoceptor (alpha1-AR) antagonist and anticholinergic agent combined therapy for patients with benign prostatic hyperplasia (BPH) together with overactive bladder (OAB) has been controversial. The purpose of this study was to evaluate the effect of tolterodine combined with alpha1-AR antagonist for patients with BPH and OAB after insufficient efficacy by monotherapy with alpha1-AR antagonist. The adverse event of this combined therapy was also assessed. The study included 47 patients with BPH, whose OAB symptom persisted (OAB symptom score; OABSS > or =3) after monotherapy with alpha1-AR antagonist for more than 4 weeks. The mean age was 72.9 years and the mean prostate volume was 29.8 ml. Four mg/day of tolterodine with alpha-AR antagonist was administered for 8 weeks to patients. International prostate symptom score (IPSS), quality of life (QOL) index, OABSS, King's Health Questionnaire (KHQ) and residual urine volume (RUV) were assessed before and after combined therapy. Six patients were dropped out from this study because of dry mouth, constipation, onset of other disease and insufficient efficacy by self-judgment. IPSS (from 15.1 +/- 6.8 to 11.0 +/- 7.9; P < 0.01), QOL index (from 4.3 +/- 1.1 to 3.6 +/- 1.3; P < 0.01) and OABSS (from 7.0 +/- 3.0 to 5.4 +/- 2.9; P < 0.01) of 41 patients improved significantly by combined therapy. The storage symptom of IPSS subscore improved significantly (from 8.0 +/- 2.9 to 6.5 +/- 2.8; P < 0.01), whereas the voiding symptom did not improve. Regarding KHQ, the score of 3 domains (impact on life, role limitation, and physical limitation) improved significantly (P < 0.05). RUV did not change and no serious adverse event including urinary retention was found in this study. This study reveals that the combined therapy of alpha-AR antagonist and tolterodine represents an effective and safe treatment modality for patients with BPH and OAB, whose OAB symptom was not improved by antecedent monotherapy with alpha-AR antagonist.


[Protective action of endogenous opioid-like peptides of different origins in duodenal ulcer in rats].
A study was made of the effects of some endogenous opioids (beta-endorphin, gamma-endorphin, met-enkephalin, leu-enkephalin and dinorphin) formed in the body from different high-molecular precursors (pro-opiomelanocortin, proenkephalins A and B) on the development in rats of the cysteamine-induced duodenal ulcers. All the peptides under study, gamma-endorphin, in particular, had an anti-ulcerous activity which was mediated by specific opiate receptors. The majority of the opioids was characterized by reduction of the anti-ulcerous effect as the dose was raised. It is assumed that protection of the duodenal mucosa under ulcerogenic exposures is an essential property of endogenous peptides. It is concluded that opioid peptides derived from different precursors are arranged in a complex synergic system responsible for cytoprotection of the duodenum.


Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic cells: potential for therapy of myeloid leukemia and myelodysplastic syndromes.
Background Aberrant or impaired repair of double-strand DNA breaks is a common feature of de novo acute myeloid leukemia and myelodysplastic syndromes. Since poly (ADP-ribose) polymerase (PARP) inhibitors have been recently shown to selectively target cells with defects in double-strand DNA repair, the aim of this study was to explore the possibility of exploiting defects in DNA repair in leukemic cells using PARP inhibitors. Leukemic cell lines were exposed to various PARP inhibitors alone and in combination with non-cytotoxic concentrations of DNA methyltransferase inhibitor, 5' aza-2'-deoxycytidine and/or the histone deacetylase inhibitor, MS275, to test for potentiation of apoptosis with these agents. PARP inhibitors, KU-0058948 and PJ34, induced cell cycle arrest and apoptosis of primary myeloid leukemic cells and myeloid leukemic cell lines in vitro. Immunofluorescence analysis also revealed that PARP inhibitor sensitivity in these leukemic cells was due to a defect in homologous recombination DNA repair. Addition of 5' aza-2'-deoxycytidine failed to increase the cytotoxicity of PARP inhibitors. In contrast, MS275 potentiated the cytotoxic effect of KU-0058948 and PJ34 in all PARP inhibitor-sensitive leukemic cells. Immunofluorescence analysis supported the idea that histone deacetylase inhibitors potentiate cytotoxicity by inhibiting DNA repair processes. Conclusions On the basis of the data presented here, we suggest that PARP inhibitors can potentially exploit defects in double-strand DNA break repair in leukemic cells, paving the way for testing the therapeutic potential of these agents in myelodysplastic syndromes and acute myeloid leukemia.


Development of a quantitative microbial risk assessment for human salmonellosis through household consumption of fresh minced pork meat in Belgium.
A quantitative microbial risk assessment (QMRA) according to the Codex Alimentarius Principles is conducted to evaluate the risk of human salmonellosis through household consumption of fresh minced pork meat in Belgium. The quantitative exposure assessment is carried out by building a modular risk model, called the METZOON-model, which covers the pork production from farm to fork. In the METZOON-model, the food production pathway is split up in six consecutive modules: (1) primary production, (2) transport and lairage, (3) slaughterhouse, (4) postprocessing, (5) distribution and storage, and (6) preparation and consumption. All the modules are developed to resemble as closely as possible the Belgian situation, making use of the available national data. Several statistical refinements and improved modeling techniques are proposed. The model produces highly realistic results. The baseline predicted number of annual salmonellosis cases is 20,513 (SD 9061.45). The risk is estimated higher for the susceptible population (estimate 4.713 x 10(-5); SD 1.466 x 10(-5)) compared to the normal population (estimate 7.704 x 10(-6); SD 5.414 x 10(-6)) and is mainly due to undercooking and to a smaller extent to cross-contamination in the kitchen via cook's hands.


Pax2 and Pax8 cooperate in mouse inner ear morphogenesis and innervation.
Pax2;5;8 transcription factors play diverse roles in vertebrate and invertebrate organogenesis, including the development of the inner ear. Past research has suggested various cochlear defects and some vestibular defects in Pax2 null mice but the details of the cochlear defects and the interaction with other Pax family members in ear development remain unclear. We show that Pax2;8 double null mice do not develop an ear past the otocyst stage and show little to no sensory as well as limited and transient neuronal development, thus indicating that these two family members are essential for overall ear morphogenesis and sustained neurosensory development. In support of functional redundancy between Pax proteins, Pax2 can be substituted by a Pax5 minigene, a gene normally not expressed in the embryonic mouse ear. There is no detectable morphological defect in Pax8 null mice suggesting that Pax2 expression can compensate for Pax8. Conversely, Pax8 cannot compensate for Pax2 leading to a cochlear phenotype not fully appreciated previously: Cochlear development is delayed until E15.5 when the cochlea extrudes as a large sack into the brain case. Immunocytochemistry and tracing from the brain show that a cochlear spiral ganglia form as a small addition to the inferior vestibular ganglion. However, the empty cochlear sack, devoid of any sensory epithelium development as indicated by the absence of Sox2 or MyoVII expression, nevertheless develop a dense innervation network of small neurons situated in the wall of the cochlear sack. Combined these data suggest that Pax2 is needed for organ of Corti formation and is directly or indirectly involved in the coordination of spiral ganglion formation which is partially disrupted in the Pax2 null ears. All three Pax genes can signal redundantly in the ear with their function being determined primarily by the spatio-temporal expression driven by the three distinct promoters of these genes.


The effectiveness of ethics education: a quasi-experimental field study.
Ethical conduct is the hallmark of excellence in engineering and scientific research, design, and practice. While undergraduate and graduate programs in these areas routinely emphasize ethical conduct, few receive formal ethics training as part of their curricula. The first purpose of this research study was to assess the relative effectiveness of ethics education in enhancing individuals' general knowledge of the responsible conduct of research practices and their level of moral reasoning. Secondly, we examined the effects of ethics education on the positive psychological outcomes of perspective-taking, moral efficacy, moral courage, and moral meaningfulness. To examine our research hypotheses, we utilized a pretest-posttest quasi-experimental design consisting of three ethics education groups (control, embedded modules, and stand-alone courses). Findings revealed that both embedded and stand alone courses were effective in enhancing participants' perspective-taking, moral efficacy, and moral courage. Moral meaningfulness was marginally enhanced for the embedded module condition. Moral judgment and knowledge of responsible conduct of research practices were not influenced by either ethics education condition. Contrary to expectations, stand alone courses were not superior to embedded modules in influencing the positive psychological outcomes investigated. Implications of these findings for future research and practice are discussed.


Microscale Strategies for Generating Cell-Encapsulating Hydrogels.
Hydrogels in which cells are encapsulated are of great potential interest for tissue engineering applications. These gels provide a structure inside which cells can spread and proliferate. Such structures benefit from controlled microarchitectures that can affect the behavior of the enclosed cells. Microfabrication-based techniques are emerging as powerful approaches to generate such cell-encapsulating hydrogel structures. In this paper we introduce common hydrogels and their crosslinking methods and review the latest microscale approaches for generation of cell containing gel particles. We specifically focus on microfluidics-based methods and on techniques such as micromolding and electrospinning.


Monogamy without parental care? Social and genetic mating systems of avian brood parasites.
Classic evolutionary theory predicts that monogamy should be intimately linked with parental care. It has long been assumed, therefore, that avian brood parasites-which lay their eggs in the nests of 'host' species and provide little, if any, parental care-should be overwhelmingly promiscuous. However, recent studies have revealed that the social mating systems of brood parasites are surprisingly diverse, encompassing lek polygyny, monogamy, polygamy and promiscuity. What ecological or phylogenetic factors explain this variation, and why are some brood parasites apparently monogamous? Here we review the social and genetic mating systems of all 75 brood parasitic species for which data are available and evaluate several hypotheses that may help explain these patterns. We find that social monogamy is widespread, often co-occurring with territoriality and cooperative behaviour by the mated pair. Comparative studies, though preliminary, suggest that in some species, monogamy is associated with low host density and polygamy with higher host density. Interestingly, molecular data show that genetic and social mating systems can be entirely decoupled: genetic monogamy can occur in parasitic species that lack behavioural pair-bonds, possibly as a by-product of territoriality; conversely, social monogamy has been reported in parasites that are genetically polygamous. This synthesis suggests that social and genetic monogamy may result from very different selective pressures, and that male-female cooperative behaviours, population density and territoriality may all interact to favour the evolution of monogamous mating in brood parasites. Given that detailed descriptive data of social, and especially genetic, mating systems are still lacking for the majority of brood parasitic species, definitive tests of these hypotheses await future work. This article is part of the theme issue 'The coevolutionary biology of brood parasitism: from mechanism to pattern'.


Differences in Corneal Biomechanics in Nonpenetrating Deep Sclerectomy and Deep Sclerectomy Reconverted into Trabeculectomy.
To evaluate the differences in intraocular pressure (IOP) and in corneal biomechanics in eyes with uneventful nonpenetrating deep sclerectomy (NPDS) in 1 eye and with intended deep sclerectomy reconverted into trabeculectomy (RIT) in the fellow eye of the same patient. Forty eyes of 20 patients with both types of glaucoma surgery and more than 6 months of follow-up, and 31 eyes of 50 controls. IOP was assessed with Goldmann applanation tonometry (GAT), ocular response analizer (ORA), and dynamic contour tonometer (DCT). Student t test for independent samples and a univariate generalized estimating equations model were used to analyze the results. Overall, no significant differences were found between IOP of NPDS and RIT eyes when measured with 3 tonometers. Although NPDS showed lower values of IOP measured with GAT and ORA, RIT presented lower IOP if DCT is the chosen tonometry. Biomechanically, NPDS eyes had higher corneal hysteresis (CH) and corneal resistance factor (CRF). When compared with control patients, eyes that underwent glaucoma surgery had lower IOP using GAT, DCT and ORA (P<0.001, 0.315, and 0.260, respectively), and lower CRF (P<0.001). Eyes with NPDS tended to have higher values of CH and CRF and lower IOP than RIT eyes, as measured with 3 of 4 tonometry methods; these differences did not reach statistical significance.


Uptake characteristics of pinocembrin and its effect on p-glycoprotein at the blood-brain barrier in in vitro cell experiments.
One purpose of the present study was to investigate the uptake characteristics of pinocembrin (PCB) and its effect on p-glycoprotein (P-gp) at the blood-brain barrier (BBB). Cultured rat brain microvascular endothelial cells (rBMECs) were used as an in vitro BBB model. Experiments were conducted to examine time-, concentration-, and temperature-dependent elements of PCB uptake, and the effect of classical P-gp inhibitors, cyclosporin A (CsA) and verapamil (Ver), on the steady-state uptake of PCB. Uptake of rhodamine 123 (Rho123), the typical P-gp substance, was measured with or without PCB. Meanwhile, the protein level of P-gp after incubation with PCB was detected by Western blot assay. The results demonstrated that PCB uptake by rBMECs was in a time- and concentration-dependent manner. CsA and Ver slightly increased PCB steady-state uptake by less than 10% (p>0.05). Similar results were observed in Rho123 uptake by co-administration of PCB. Further results were obtained by Western blot assay. PCB might not affect P-gp expression in rBMECs. Overall, the findings demonstrate that the passive transport process may be the main process for PCB to pass through the BBB, and P-gp is likely to have a little effect on the PCB transport process. Furthermore, PCB may not affect the functional activity and the protein expression of the P-gp transporter at the BBB.


Sulindac modulates secreted protein expression from LIM1215 colon carcinoma cells prior to apoptosis.
Colorectal cancer (CRC) is a major cause of mortality in Western populations. Growing evidence from human and rodent studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) cause regression of existing colon tumors and act as effective chemopreventive agents in sporadic colon tumor formation. Although much is known about the action of the NSAID sulindac, especially its role in inducing apoptosis, mechanisms underlying these effects is poorly understood. In previous secretome-based proteomic studies using 2D-DIGE/MS and cytokine arrays we identified over 150 proteins released from the CRC cell line LIM1215 whose expression levels were dysregulated by treatment with 1mM sulindac over 16h; many of these proteins are implicated in molecular and cellular functions such as cell proliferation, differentiation, adhesion, angiogenesis and apoptosis (Ji et al., Proteomics Clin. Appl. 2009, 3, 433-451). We have extended these studies and describe here an improved protein/peptide separation strategy that facilitated the identification of 987 proteins and peptides released from LIM1215 cells following 1mM sulindac treatment for 8h preceding the onset of apoptosis. This peptidome separation strategy involved fractional centrifugal ultrafiltration of concentrated cell culture media (CM) using nominal molecular weight membrane filters (NMWL 30K, 3K and 1K). Proteins isolated in the >30K and 3-30K fractions were electrophoretically separated by SDS-PAGE and endogenous peptides in the 1-3K membrane filter were fractioned by RP-HPLC; isolated proteins and peptides were identified by nanoLC-MS-MS. Collectively, our data show that LIM1215 cells treated with 1mM sulindac for 8h secrete decreased levels of proteins associated with extracellular matrix remodeling (e.g., collagens, perlecan, syndecans, filamins, dyneins, metalloproteinases and endopeptidases), cell adhesion (e.g., cadherins, integrins, laminins) and mucosal maintenance (e.g., glycoprotein 340 and mucins 5AC, 6, and 13). A salient finding of this study was the increased proteolysis of cell surface proteins following treatment with sulindac for 8h (40% higher than from untreated LIM1215 cells); several of these endogenous peptides contained C-terminal amino acids from transmembrane domains indicative of regulated intramembrane proteolysis (RIP). Taken together these results indicate that during the early-stage onset of sulindac-induced apoptosis (evidenced by increased annexin V binding, dephosphorylation of focal adhesion kinase (FAK), and cleavage of caspase-3), 1mM sulindac treatment of LIM1215 cells results in decreased expression of secreted proteins implicated in ECM remodeling, mucosal maintenance and cell-cell-adhesion. This article is part of a Special Issue entitled: An Updated Secretome.


Pathogenesis of disease caused by Entamoeba histolytica: studies of adherence, secreted toxins, and contact-dependent cytolysis.
Amebiasis is due to invasion of the colonic mucosa by the enteric protozoan Entamoeba histolytica. The biology of the parasite and the pathogenic mechanisms of E. histolytica have been extensively studied. Recent studies provide new insights into the mechanism by which amebas colonize the gut, interact with bacterial flora, adhere to and lyse tissue, and combat the host's inflammatory response. Elucidation of the biochemical and cellular bases of the pathogenesis of disease caused by E. histolytica may lead to the development of an immunologic or pharmacologic means of prophylaxis.


Nanotechnology and Osteoarthritis. Part 2: Opportunities for advanced devices and therapeutics.
Osteoarthritis (OA) is a multifactorial disease of the entire joint which afflicts 140 million individuals worldwide regardless of economic or social status. Current clinical treatments for OA primarily center on reducing pain and increasing mobility, and there are limited therapeutic interventions to restore degraded cartilage or slow disease pathogenesis. This second installment of a two-part review on nanotechnology and OA focuses on novel treatment strategies. Specifically, Part 2 first discusses current surgical and nonsurgical treatments for OA and then summarizes recent advancements in nanotechnology-based treatments, while Part 1 (10.1002/jor.24817) described advances in imaging and diagnostics. We review nano delivery systems for small molecule drugs, nucleic acids, and proteins followed by nano-based scaffolds for neocartilage formation and osteochondral regeneration, and lastly nanoparticle lubricants. We conclude by identifying opportunities for nanomedicine advances, and prospects for OA treatments.


Emergency department attendances and GP patient satisfaction.
Despite invaluable national data, reasons for the relentless rise in England's emergency department (ED) attendances remain elusive. All EDs and general practices in England. Are rising ED attendances related to general practice patient satisfaction, i.e. if patients are unable to get a convenient appointment with their general practitioner (GP), then do they attend their local ED for diagnosis, treatment and care instead? GP patient satisfaction and ED attendance data were extracted from national data warehouses and organised into two groups: (i) England clinical commissioning group (CCG) areas and (ii) a London CCG subset. Data from London CCGs were compared with CCGs outside London. ED attendances were strongly correlated with GP patient satisfaction data in non-London CCGs, e.g. if patients said they had difficulty obtaining a convenient appointment at their general practice, then local ED attendances increased. Associations were repeated when other GP perception data were explored, e.g. if patients were satisfied with GPs and practice nurses, then they were less likely to attend their local EDs. However, these associations were not found in the London CCG subset despite lower satisfaction with London GP services. Although our study generates valuable insights into ED attendances, the reasons why London general practice patient and ED attendance data don't show the same associations found outside London warrants further study. Diverting patients from EDs to primary care services may not be straight forward as many would like to believe.


Primary role of CYP1B1 in Indian juvenile-onset POAG patients.
CYP1B1, a member of the cytochrome P450 superfamily of enzymes, has been implicated in primary congenital glaucoma (PCG). Recent studies suggest a role of CYP1B1 in primary open-angle glaucoma (POAG) as a modifier locus. The purpose of the study was to further investigate the potential role of CYP1B1 in POAG patients. Two hundred unrelated Indian POAG patients and 100 unrelated ethnically matched controls were enrolled in this study. The coding sequence of CYP1B1 was amplified by polymerase chain reaction (PCR) from genomic DNA, followed by direct DNA sequencing to identify the allelic variants. Six mutations were identified in nine patients and none of the controls examined. One novel mutation (R523T) was detected in the homozygous condition while three reported (W57C, E229K, and R368H) and two novel mutations (S515L and D530G) were found in the heterozygous state. The homozygous mutation of a conserved residue, detected in a familial juvenile onset POAG (JOAG) patient (lacking MYOC or OPTN mutations), cosegregated with the disease locus in an autosomal recessive mode of transmission. All the novel mutations (R523T, S515L and D530G) were detected in a region of CYP1B1 that did not harbor any of the 34 point mutations implicated in PCG. In addition, six previously reported (p.R48G, p.A119S, p.V432L, p.D449D, p.N453S, and 372-12C>T in intron 1) and four novel (p.V395V, p.P400P, p.V518A, and c.2016C>G in the 3'-UTR) single nucleotide polymorphism (SNPs) were also observed in POAG patients and controls. Our observation suggests that on rare occasions CYP1B1 may be primarily responsible for JOAG by possible monogenic association, and this observation emphasizes the importance of screening for mutation in this gene of JOAG patients that are determined not to harbor mutations in previously characterized candidate genes and loci for POAG.


The health of health care workers. The Ernestine Henry lecture 1990.
The health of health care workers is mentioned in the early occupational health literature but the significance of these populations in occupational health has only recently received widespread attention. The health care industry now employs about 5% of the national workforce and, despite its size and the multiplicity of its occupational hazards, little systematic enquiry has taken place to quantify these risks. The occupational health services available to health service staff are often rudimentary. Current health concerns include evidence that the mortality experience of subgroups is not as favourable as for comparable socio-economic groups. Specific areas of concern are occupational exposures to biological agents such as HIV and hepatitis B, pharmaceutical products, allergens, violence, electromagnetic fields and chemical carcinogens. Psychosocial factors and excessive hours of work may, in part, explain the high suicide rates experienced by some subsections of the workforce. New initiatives to investigate and monitor this complex working environment are clearly needed.


Spectroscopic investigations of the binding interaction of a new indanedione derivative with human and bovine serum albumins.
Binding of a newly synthesized indanedione derivative, 2-(2-hydroxy-3-ethoxybenzylidene)-1,3-indanedione (HEBID), to human and bovine serum albumins (HSA and BSA), under simulated physiological conditions was monitored by fluorescence spectroscopy. The binding parameters (binding constants and number of binding sites) and quenching constants were determined according to literature models. The quenching mechanism was assigned to a Förster non-radiative energy transfer due to the HEBID-SA complex formation. A slightly increased affinity of HEBID for HSA was found, while the number of binding sites is approximately one for both albumins. The molecular distance between donor (albumin) and acceptor (HEBID) and the energy transfer efficiency were estimated, in the view of Förster's theory. The effect of HEBID on the protein conformation was investigated using circular dichroism and synchronous fluorescence spectroscopies. The results revealed partial unfolding in the albumins upon interaction, as well as changes in the local polarity around the tryptophan residues.


Endemic goitre in Chinamora, Zimbabwe. The Chinamora Research Team.
In a survey of 3841 rural dwellers in Chinamora, Zimbabwe, goitre was found in 29%. There was associated moderate iodine deficiency, and 8 people out of a subgroup of 229 had biochemical myxoedema; 2 others had biochemical thyrotoxicosis. Thyrotropin levels were not raised in 100 children aged less than one year. There did not seem to be a role for goitrogens in the pathogenesis of the goitres. A nationwide iodinisation programme should be introduced in Zimbabwe.


Evaluation of the effect of home bleaching agents on surface microhardness of different glass-ionomer cements containing hydroxyapatite.
Home bleaching agents may exert some negative effects on surface hardness of restorative materials such as glass-ionomer cements (GICs). Since some studies have shown that some components such as hydroxyapatite (HA), as a bioactive glass, can improve the mechanical properties of dental materials, the effect of bleaching agents on surface hardness of GICs containing hydroxyapatite is questionable. This study was designed to evaluate the effect of home bleaching agents on the surface hardness of two different commercially available GICs containing hydroxyapatite. 80 disk-shaped specimens were made from two different GICs, including resin modified glass-ionomer and Zirconomer. Each material was divided into four groups (n=10): 1. control, 2. 20 %wt. hydroxyapatite-containing, 3. bleached and 4. bleached 20 %wt. hydroxyapatite-containing. Group 1 and 2 specimens were stored in distilled water for 2 weeks while group 3 and 4 specimens were treated with 15% carbamide peroxide in that period. Surface hardness was tested with Vickers surface hardness tester. Data were analyzed with 3-way ANOVA and mean comparison done by post hoc Tukey tests (p<0.05). In general RMGI had a significantly highest Vickers surface hardness value among all groups. 15% carbamide peroxide reduced surface hardness compared to control groups (RMGI and Zr) significantly. In the HA-containing GICs groups, bleaching agent did not significantly changed the surface hardness value. In this study we concluded that applied treatments (bleaching and adding HA) in implicit percentages reduced surface hardness of GICs. Also we suggest more studies in clinical conditions be done to verify these results. Key words:Home bleaching, Resin Modified Glass-ionomer cement, surface hardness, Zirconia-reinforced glass ionomer, hydroxyapatite.


Sensitive determination of phenolic acids in extra-virgin olive oil by capillary zone electrophoresis.
A sensitive, rapid, efficient, and reliable method for the separation and determination of phenolic acids by capillary zone electrophoresis has been carried out. A detailed method optimization was carried out to separate 14 different compounds by studying parameters such as pH, type and concentration of buffer, applied voltage, and injection time. The separation was performed within 16 min, using a 25 mM sodium borate buffer (pH 9.6) at 25 kV with 8 s of hydrodynamic injection. With this method and using a liquid-liquid extraction system, with recovery values around 95%, it has been possible to detect small quantities of phenolic acids in olive oil samples. This is apparently the first paper showing the quantification of this specific family of phenolic compounds in virgin olive oil samples.


Arugomycin, a new anthracycline antibiotic. II. Structural elucidation.
The structure of arugomycin was determined by chemical degradation, and NMR and mass spectral analyses to be a new anthracycline antibiotic with arugorol (4'-epi-nogalarol) as the chromophore and two sugar chains comprising diginosyl-decilonitrosyl-2-deoxyfucose, and (4-O-fumaryl-diginosyl)-diginosyl-2-deoxyfucosyl -diginose.


[Identical results of primary percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction admitted as a result of direct or indirect referral].
Description of the results of primary percutaneous transluminal coronary angioplasty (PTCA) in the management of acute myocardial infarction. Prospective, descriptive. Data were collected on case record forms of consecutive patients with an acute myocardial infarction who in 1990-1997 were referred for primary PTCA directly to Hospital De Weezenlanden, Zwolle, the Netherlands, or indirectly from another hospital. Patients to be considered numbered 1296, 1004 males and 292 females, with a mean age of 60 years. The number of patients increased markedly in the course of the study period. Patients referred by another hospital more often had anterior wall myocardial infarction (73% as against 42%) or cardiogenic shock (10% as against 7%). A total of 1187 (92%) patients underwent primary PTCA, 46 (4%) an emergency bypass operation and 63 (5%) only pharmacotherapy. Transportation from a referring hospital lasted a median of 70 minutes, but for patients in De Weezenlanden it took 15 minutes more to arrive in the hospital, and 30 minutes more between admission and PTCA. The mortality within 30 days was low in both groups (referred from another hospital: 7%; transported immediately to De Weezenlanden: 5%); the same was true of the risk of a recurrent infarction within 30 days (2% and 1%). Cardiogenic shock was associated with higher mortality (32% and 38%). Primary PTCA as therapy for acute myocardial infarction can be applied in routine clinical practice.


[The changes of glucocorticoid receptor and beta-adrenoreceptor of lung tissues in SD rat asthma models and the effects of antiasthmatics on them].
To observe the changes of glucocorticoid receptor (GR) and beta-adrenoreceptor (beta-AR) of lung tissue and the effects of oral procaterol, salbutamol and intraperitoneal (i.p.) or inhaled (i.h.) dexamethasone (Dex). The GR or beta-AR were determined by using 3H-dexamethasone and 3H-Dihydroalprenolol as ligand respectively, in groups of rat asthma models at 1, 3, 7, 14th day and groups received antiasthmatics on the 7th day after daily consecutive challenges. The GR Bmax of asthma groups increased significantly after the first challenge, but decreased since the third day to a lower level than that of healthy control. The KD also decreased significantly since the third day. The beta-AR Bmax of asthma group gradually decreased to a significant low level on the 14th day. The Dex i.p. group had the lowest GR Bmax and the Dex i.h. group had the highest beta-AR Bmax among the treated. In the procaterol and salbutamol group, there had no decrease of GR Bmax compared with that of controls. The GR and beta-AR levels of lung tissues changed after daily challenges. The GC played a down-regulation role on GR and an up-regulation role on beta-AR in lung tissues. The Dex i.h. had more advantages than Dex i.p. in terms of GR and beta-AR regulations.


The Effects of Sodium Citrate Ingestion on Metabolism and 1500-m Racing Time in Trained Female Runners.
The purpose of the study was to assess the effects of sodium citrate ingestion on the metabolic response to exercise and performance in a 1500-m competitive run in trained female middle-distance runners in field conditions. Seventeen athletes (mean (± SD) aged 18.6 ± 2.5 years, VO2max 55.2 ± 7.6 ml·kg(-1)·min(-1)) competed in two 1500-m races following ingestion of 0.4 g·kg(-1) body mass of sodium citrate (CIT) and placebo (PLC - 1.0% solution of NaCl). The two substances, CIT and PLC were administered in 800 ml of solution in a randomly assigned double-blind crossover manner. Capillary blood samples were analysed for lactate, glucose, haemoglobin and haematocrit before administering the solutions (baseline) as well as before and after both 1500-m races. The athletes' times for trials CIT and PLC were 321.4 ± 26.4 and 317.4 ± 22.5 s, respectively (p > 0.05). A greater relative increase in plasma volume after administering the experimental solution, an increased body mass (by 0.4 kg; p = 0.006) immediately before the race and a restrained increase in blood glucose concentration (by 2.5 ± 1.2 mmol·l(-1) vs 3.4 ± 0.8 mmol·l(-1); p = 0.002) during the race were observed in the CIT trial compared to the PLC. A significant relationship was observed between body mass of the subjects immediately before the race and performance time (r = 0.374; p = 0.029). There were no between-treatment differences in heart rate in any stage of the run or in blood lactate accumulation during the race (final concentration of lactate was 14.4 ± 3.0 mmol·l(-1) and 13.4 ± 2.5 mmol·l(-1) (p > 0.05) in the CIT and PLC trials, respectively). The results suggest that sodium citrate induces an increase in water retention before exercise and may modify carbohydrate metabolism in high intensity running, but does not improve performance in 1500-m competitive run in female middle-distance runners. Key pointsPrevious studies have found that sodium bicarbonate administration may enhance performance in male athletes in running distances of 400-1500 m.The use of sodium bicarbonate in competitive sports is limited because it induces gastrointestinal distress in many subjects.The limited data on the effects of sodium citrate ingestion on the metabolic response to exercise and performance suggest that it may have all the benefits of sodium bicarbonate without the associated negative side effects.We assessed the effects of sodium citrate ingestion on the metabolic response to exercise and performance in a 1500-m competitive run in trained young female middle-distance runners.The results suggest that sodium citrate induces an increase in water retention before exercise and may modify carbohydrate metabolism in high intensity running, but does not improve performance in 1500-m competitive run in female middle-distance runners.


Stomatal Development and Perspectives toward Agricultural Improvement.
Stomata are small pores on the surface of land plants that facilitate gas exchange-acquiring CO2 from surrounding atmosphere and releasing water vapor. In adverse conditions, such as drought, stomata close to minimize water loss. The activities of stomata are vital for plant growth and survival. In the last two decades, key players for stomatal development have been discovered thanks to the model plant Arabidopsis thaliana Our knowledge about the formation of stomata and their response to environmental changes are accumulating. In this review, we summarize the genetic and molecular mechanisms of stomatal development, with specific emphasis on recent findings and potential applications toward enhancing the sustainability of agriculture.


Screening and combination selection of multifunctional actinomycetes for aerobic composting.
With the development of animal husbandry in China, the production of a large amount of livestock and poultry manure has become one of the main agricultural pollution sources. High-temperature aerobic composting stands out as one of the most crucial methods for the safe and resourceful utilization of livestock and poultry manure, serving as an essential link between crop cultivation, animal breeding, and sustainable agricultural development. Numerous studies have demonstrated that the addition of exogenous multifunctional bacterial agents to compost reduces not only harmful emissions but also sequesters or increases essential nutrients. However, these efficacies depend on the specific functions of the bacteriophage itself, the harmonization and complementarity within the colony, and its ability to adapt to the environment. In recent years, relatively few studies have been conducted on actinomycetes. This experiment provides excellent actinomycete resources for the production of high-efficiency and high-quality compost compound microbial agents of manure and straw.


Exceptionally High Electric Double Layer Capacitances of Oligomeric Ionic Liquids.
Electric double layer (EDL) capacitors are promising as next-generation energy accumulators if their capacitances and operation voltages are both high. However, only few electrolytes can simultaneously fulfill these two requisites. Here we report that an oligomeric ionic liquid such as IL4TFSI with four imidazolium ion units in its structure provides a wide electrochemical window of ∼5.0 V, similar to monomeric ionic liquids. Furthermore, electrochemical impedance measurements using Au working electrodes demonstrated that IL4TFSI exhibits an exceptionally high EDL capacitance of ∼66 μF/cm2, which is ∼6 times as high as those of monomeric ionic liquids so far reported. We also found that an EDL-based field effect transistor (FET) using IL4TFSI as a gate dielectric material and SrTiO3 as a channel material displays a very sharp transfer curve with an enhanced carrier accumulation capability of ∼64 μF/cm2, as determined by Hall-effect measurements.


Effect of additives on the renaturation of reduced lysozyme in the presence of 4 M urea.
Reduced lysozyme was renatured by sulfhydryl-disulfide interchange reactions at pH 8.0 in the presence of 4 M urea, with or without additives at 40 degrees C. In the absence of additives, the final folding yield of reduced lysozyme was approximately 40%. In the presence of sarcosine, glycerol, ammonium sulfate, N-acetyl glucosamine and glucose, its folding yields increased in all cases. In particular, yields increased up to 90% in the presence of 4 M sarcosine. On the other hand, the melting temperatures of lysozyme with or without additives in 0.02 M citrate buffer (pH 6.0) were evaluated using differential scanning calorimetry. In the absence of additive, the melting temperature of lysozyme was 73.8 degrees C. In the presence of additives, all melting temperatures were higher than that of lysozyme in the absence of additives. Moreover, there was a good correlation on addition of additives between an increase in the folding yield of reduced lysozyme with 4 M urea and an increase in the melting temperature without 4 M urea. Therefore, we conclude that additives, which stabilize native lysozyme, are effective at increasing the folding yield of reduced lysozyme in 4 M urea.


Untargeted Headspace-Gas Chromatography-Ion Mobility Spectrometry in Combination with Chemometrics for Detecting the Age of Chinese Liquor (Baijiu).
This paper proposes the combination of headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and chemometrics as a method to detect the age of Chinese liquor (Baijiu). Headspace conditions were optimized through single-factor optimization experiments. The optimal sample preparation involved diluting Baijiu with saturated brine to 15% alcohol by volume. The sample was equilibrated at 70 °C for 30 min, and then analyzed with 200 μL of headspace gas. A total of 39 Baijiu samples from different vintages (1998-2019) were collected directly from pottery jars and analyzed using HS-GC-IMS. Partial least squares regression (PLSR) analysis was used to establish two discriminant models based on the 212 signal peaks and the 93 identified compounds. Although both models were valid, the model based on the 93 identified compounds discriminated the ages of the samples more accurately according to the goodness of fit value (R2) and the root mean square error of prediction (RMSEP), which were 0.9986 and 0.244, respectively. Nineteen compounds with variable importance for prediction (VIP) scores > 1, including 11 esters, 4 alcohols, and 4 aldehydes, played vital roles in the model established by the 93 identified compounds. Overall, we determined that HS-GC-IMS combined with PLSR could serve as a rapid and accurate method for detecting the age of Baijiu.


Effect of Water Deficits on Seed Development in Soybean : II. Conservation of Seed Growth Rate.
Water deficits during seed filling decrease seed size in soybean (Glycine max L.). This may result from a reduction in the supply of assimilates from the maternal plant and/or an inhibition of seed metabolism. To determine whether maternal or zygotic factors limited seed growth, we examined the effects of a plant water deficit on the supply of sucrose to and its utilization by developing embryos. Plants were grown in the greenhouse, and water deficits were imposed by withholding water for a period of 6 days during linear seed fill. When water was withheld, leaf water potential decreased rapidly, inhibiting canopy photosynthesis completely within 3 days. However, seed dry weight (nodes 7-11) continued to increase at or near the control rate. The level of total extractable carbohydrates in leaf, stem, and pericarp tissue decreased by 70, 50, and 45%, respectively, indicating that reserves were mobilized to support seed growth. Cotyledon sucrose content decreased from about 60 milligrams per gram dry weight to 30 milligrams per gram dry weight. Similarly, the concentration of sucrose in the interfacial apoplast of the cotyledons decreased from approximately 100 millimolar to 50 millimolar. However, the rate of sucrose accumulation by excised embryos, measured in a short-term in vitro assay, increased in response to the water deficit. These results indicate that both source and sink activity in soybean are altered by water deficits to maintain the flux of assimilates to the developing embryos. This may explain why seed growth is maintained, albeit for a shorter duration, when soybean is exposed to water deficits during the seed filling period.


Strategies to optimize protein expression in E. coli.
Recombinant protein expression in Escherichia coli (E. coli) is simple, fast, inexpensive, and robust, with the expressed protein comprising up to 50 percent of the total cellular protein. However, it also has disadvantages. For example, the rapidity of bacterial protein expression often results in unfolded/misfolded proteins, especially for heterologous proteins that require longer times and/or molecular chaperones to fold correctly. In addition, the highly reductive environment of the bacterial cytosol and the inability of E. coli to perform several eukaryotic post-translational modifications results in the insoluble expression of proteins that require these modifications for folding and activity. Fortunately, multiple, novel reagents and techniques have been developed that allow for the efficient, soluble production of a diverse range of heterologous proteins in E. coli. This overview describes variables at each stage of a protein expression experiment that can influence solubility and offers a summary of strategies used to optimize soluble expression in E. coli.


The future of research into growth hormone responsiveness.
Decades of experience with growth hormone (GH) therapy have indicated considerable variability in responsiveness to therapy, even within single diagnostic categories, such as GH deficiency, Turner syndrome, intrauterine growth retardation and idiopathic short stature. It is likely that the major explanation for such variability lies in the genetic composition of the patient, including mutations of genes participating in the GH-insulin growth factor I cascade and genetic polymorphisms. Future studies of pharmacogenomic and pharmacoproteomic markers may allow us to better predict and categorize responsiveness to therapy.


[Effects of Electroacupuncture on Hippocampal nNOS Expression in Rats with Anxiety-like Behavior].
To compare the effects of electroacupuncture (EA) preconditioning and post-conditioning on hippocampal neuronal nitric oxide synthase (nNOS) expression in rats with anxiety-like behavior, so as to explore the reasonable EA intervention time. Forty-two SD rats were randomly divided into 6 groups:normal 1, normal 2, anxiety model 1, an-xiety model 2, EA-pre-conditioning and EA-post-conditioning. The anxiety model was established by giving the rats with repeated foot shock stimulation (0.8 mA, 2-25 s/time, 10 times in 5 min) combined with isolation-raising. Before or after modeling, EA stimulation was applied to "Baihui" (GV 20) and "Yintang" (GV 29) for 20 min, once a day for 7 days. Elevated plus maze (EPM) tests were performed to determine the percentages of time spent in the open arms and the percentages of entries into the open arms in 5 min for evaluating the animals' anxiety-like behavioral activities. The reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect hippocampal nNOS mRNA expression and the immunohistochemical staining adopted to detect the expression of nNOS protein in the hippocampal CA 1 and CA 3 areas, respectively. Compared with their own normal control group 1 and 2, both the percentage of time spent in the open arms and the percentage of entries into the open arms were significantly decreased in model group 1 and 2 (P<0.05, P<0.01). After pre- and post-conditioning of EA, the decreased proportions of time spent and entries into the open arms were considerably increased (P<0.05), suggesting an improvement of anxiety-like behavior activities after EA intervention. The expression levels of hippocampal nNOS mRNA and nNOS protein in the hippocampal CA 3 region were significantly higher in the model group 1 and 2 than in their own normal control group 1 and 2 (P<0.01), but those of nNOS protein in the CA 1 area were markedly lower in the model group 1 and 2 than in their own normal control group 1 and 2 (P<0.01). Following pre- and post-conditioning of EA, the increased expression levels of nNOS mRNA and protein of CA 3 area and the decreased level of nNOS protein of CA 1 area were all notably reversed (P<0.05, P<0.01). Both pre- and post-conditioning of EA can improve anxiety-like behavior in anxiety rats, which may be associated with its effects in down-regulating hippocampal nNOS expression.


Possibility of chemoprevention by the eradication of Helicobacter pylori: oxidative DNA damage and apoptosis in H. pylori infection.
The purpose of this study was to study the changes of 8-hydroxydeoxyguanosine (8-OH-dG) contents of DNA from human gastric mucosa with or without Helicobacter pylori and the changes of two biomarkers, iNOS and apoptosis, in gastric biopsies obtained before and after the eradication of H. pylori. DNA isolated from the biopsied human gastric mucosa was digested to deoxynucleotides by nuclease P1, then with Escherichia coli alkaline phosphatase, and analyzed by HPLC-ECD system. 8-OH-dG content was expressed as the number of residues per 10(5) deoxyguanosine. iNOS immunohistochemical staining was performed with antihuman iNOS antiserum generated in mice at a dilution of 1:500, and in situ apoptosis was detected by in situ terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling. Both the density of H. pylori and the degree of inflammation were scored. The 8-OH-dG contents of healthy normal controls with negative H. pylori were 4.31 +/- 2.33 (8-OH-dG/10(5) dG), whereas those of patients with positive H. pylori were 10.40 +/- 7.25. The difference between these two values was statistically significant (p < 0.01). The 8-OH-dG contents were significantly decreased after the eradication of H. pylori (12.22 +/- 2.09 vs. 2.42 +/- 1.22, p < 0.001). After the eradication of H. pylori, both the apoptotic index and the iNOS scores were significantly decreased, compared with those before eradication (3.72 +/- 1.74 vs. 1.17 +/- 1.06 for apoptosis and 10.34 +/- 6.79 vs. 1.43 +/- 1.14 for iNOS, p < 0.001). Statistically significant correlations were observed among apoptotic index, iNOS score, degree of inflammation, and density of H. pylori (p < 0.05). The increased levels of oxidative DNA damage, increased occurrences of apoptosis, and increased expressions of iNOS suggest mechanistic links between H. pylori infection and gastric carcinogenesis.


Vascular Cell Co-Culture on Silk Fibroin Matrix.
Silk fibroin (SF), a natural polymer material possessing excellent biocompatibility and biodegradability, and has been widely used in biomedical applications. In order to explore the behavior of vascular cells by co-culturing on regenerated SF matrix for use as artificial blood vessels, human aorta vascular smooth muscle cells (HAVSMCs) were co-cultured with human arterial fibroblasts (HAFs) or human umbilical vein endothelial cells (HUVECs) on SF films and SF tubular scaffolds (SFTSs). Analysis of cell morphology and deoxyribonucleic acid (DNA) content showed that HUVECs, HAVSMCs and HAFs adhered and spread well, and exhibited high proliferative activity whether cultured alone or in co-culture. Immunofluorescence and scanning electron microscopy (SEM) analysis showed that HUVECs and HAFs co-existed well with HAVSMCs on SF films or SFTSs. Cytokine expression determined by reverse transcription-polymerase chain reaction (RT-PCR) indicated that the expression levels of α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-MHC) in HAVSMCs were inhibited on SF films or SFTSs, but expression could be obviously promoted by co-culture with HUVECs or HAFs, especially that of SM-MHC. On SF films, the expression of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD31) in HUVECs was promoted, and the expression levels of both increased obviously when co-cultured with HAVSMCs, with the expression levels of VEGF increasing with increasing incubation time. The expression levels of VEGF and CD31 in cells co-cultured on SFTSs improved significantly from day 3 compared with the mono-culture group. These results were beneficial to the mechanism analysis on vascular cell colonization and vascular tissue repair after in vivo transplantation of SFTSs.


Evidence for the in-vitro de-novo synthesis of immunoglobulin and a previously undescribed 17 kDa protein (TEP-2) by the mucosa of the fallopian tube.
De-novo synthesis and secretion of proteins by short-term explants of matched Fallopian tube mucosa and endometrium were studied using radiolabelled L-[35S]methionine and [3H]glucosamine. To compare directly each anatomical site of the Fallopian tube and endometrium from the same source, newly synthesized proteins were separated on one-dimensional polyacrylamide gel electrophoresis and examined by auto-radiography. De-novo synthesis of two protein bands provisionally designated as tubal epithelial protein 1 (TEP-1) and tubal epithelial protein 2 (TEP-2), was observed in explants of the Fallopian tube mucosa obtained from each anatomical site throughout the ovarian cycle (n = 20). TEP-2 was not apparent in tubal mucosa obtained from post-menopausal women (n = 5). De-novo synthesis of TEP-1 and TEP-2 was not apparent in autoradiographs of radiolabelled proteins from short-term explants of endometrium. From the autoradiographs the molecular mass of TEP-1 and TEP-2 was calculated to be 25 kDa and 17 kDa, respectively. Incorporation of glucosamine into newly synthesized protein occurred in TEP-2 but not TEP-1. TEP-1 was observed to be immunochemically identical to immunoglobulin kappa light chains.


A PEG-based biocompatible block catiomer with high buffering capacity for the construction of polyplex micelles showing efficient gene transfer toward primary cells.
Nonviral gene vectors from synthetic catiomers (polyplexes) are a promising alternative to viral vectors. In particular, many recent efforts have been devoted to the construction of biocompatible polyplexes for in vivo nonviral gene therapy. A promising approach in this regard is the use of poly(ethylene glycol) (PEG)-based block catiomers, which form a nanoscaled core-shell polyplex with biocompatible PEG palisades. In this study, a series of PEG-based block catiomers with different amine functionalities were newly prepared by a simple and affordable synthetic procedure based on an aminolysis reaction, and their utility as gene carriers was investigated. This study revealed that the block catiomers carrying the ethylenediamine unit at the side chain are capable of efficient and less toxic transfection even toward primary cells, highlighting critical structural factors of the cationic units in the construction of polyplex-type gene vectors. Moreover, the availability of the polyplex micelle for transfection with primary osteoblasts will facilitate its use for bone regeneration in vivo mediated by nonviral gene transfection.


The Role of Occupational Therapy in Managing Food Selectivity of Children with Autism Spectrum Disorder: A Scoping Review.
Food selectivity is common in children with autism spectrum disorder (ASD). It can be defined as the unwillingness to eat common or new foods, resulting in a lack of variety in the diet or limited food consumption for multiple reasons, such as inflexibility or sensory alterations. We conducted a peer scoping review to describe the interventions that are carried out from occupational therapy (OT) in children with ASD with food selectivity. Two authors independently searched the databases PubMed, Scopus, Web of Science, and EMBASE, as well as the OT journals indexed in Journal Citation Reports. Articles exploring OT interventions in children (≤12 years) with ASD and food selectivity, published in Spanish or English, with experimental design, and with full text available were included. Of the 1445 articles identified, 8 articles met the inclusion criteria. Three main intervention categories were identified: sensory-behavioral, family focused, and other interventions. Most of the interventions from OT were aimed at treating sensory-behavioral aspects. Only three articles described interventions led exclusively by occupational therapists, and the rest were led by a multidisciplinary team. Finally, although these interventions are not exclusive to OT, occupational therapists can participate together with other professionals as an essential component in the treatment of food selectivity in children with ASD.


Clinical Performance of a Powered Surgical Stapler for Left Atrial Appendage Resection in a Video-Assisted Thoracoscopic Ablation for Patients with Nonvalvular Atrial Fibrillation.
Left atrial appendage (LAA) has been found to be associated with the occurrence of thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Stapling exclusion of LAA during surgical ablation could be an alternative to oral anticoagulation for NVAF patients. However, its safety and efficacy have rarely been examined. Thus, in this study, we aimed to evaluate the safety and efficacy of a powered surgical stapler for LAA resection during ablation for patients with NVAF.Adult patients with NVAF undergoing stapler surgery were included in this study. LAAs of patients were cut off using a powered surgical stapler. Intraoperative transesophageal echocardiogram (TEE) was applied before and after the operation. Each patient received anticoagulant therapy for 2 months after surgery and was regularly followed up by appointment or via telephone call. Patients would undergo physical examinations, echocardiography, and 24-hour dynamic electrocardiogram in a local or in our hospital to determine whether there was a recurrence of atrial fibrillation (AF) or thromboembolism caused by AF.In total, 124 patients were included in this study (male: 88 (71.0%); mean age: 62.3 years). Blood loss was less than 100 mL in all patients with no operative complications or hospital deaths. Moreover, 119 (96.0%) follow-up data were collected, with a mean period of 27.4 months. All patients discontinued oral anticoagulants 2 months after their operation. As per our findings, AF recurred in 23 patients (18.5%), with an average of 9.1 months after surgery. No patients were diagnosed with thromboembolism related to AF.Stapling exclusion of LAA during surgical ablation could safely and completely resect the LAA. The effect of thrombus prevention was deemed satisfactory.


Sertraline for the treatment of depression in Parkinson's disease.
Although antidepressant medications are commonly used to treat depression in Parkinson's disease (PD), little information is available regarding their safety and efficacy in this condition. Sertraline is a relatively selective serotonin reuptake inhibitor with some dopamine reuptake inhibitor activity. It has a favorable tolerability profile, especially in the elderly. We undertook an open-label pilot evaluation of the safety and efficacy of sertraline to treat depression in PD. A total of 15 patients with PD and depression participated in the study. Sertraline was introduced at a daily dose of 25 mg for 1 week and then increased to 50 mg/day. Patients underwent evaluation at baseline and at a final visit approximately 7 weeks later. Sertraline was generally well tolerated, but five patients experienced side effects, and two discontinued medication. Patients taking selegiline experienced more adverse effects. Beck Depression Inventory scores improved significantly (mean +/- SE = 16.0 +/- 2.0 vs 11.7 +/- 1.9, p = 0.03), and Unified Parkinson's Disease Rating Scale and energy-level scores were unchanged. These results suggest that sertraline may be a useful treatment for depression in PD. As substantial placebo effects can occur in studies of PD and depression, placebo-controlled, double-blind studies are warranted.


Epidemiology / vaccine efficacy trials. "HIV Incidence in Adults in Northern Thailand".
According to an abstract submitted by the authors to the X International Conference on AIDS, held August 7-12, 1994, in Yokohama, Japan, " To measure the HIV-1 incidence, follow-up rates and high risk behaviors in cohorts of seronegative adults in northern Thailand. We screened cohorts of female commercial sex workers (CSWs), male STD clinic patients, Royal Thai Army (RTA) conscripts, and discharged RTA conscripts at baseline and q3 to 6 months for HIV infection by ELISA and WB and did interviews for high risk behavior, medical history, and STD cultures. Of 1068 CSWs, 409 (38.3%) were HIV positive, and 396 HIV negative were enrolled in the study; follow-up at 6 months was 70.7% and 19 seroconverted, for an incidence of 12.8/100 person years. Of 1031 male STD patients, 164 (15.9%) were HIV positive, and 264 HIV negative (30.4%) were enrolled; follow-up at 6 months was 91.9% and 6 seroconverted, for an incidence of 4.92/100 person years. Of 969 RTA conscripts, 12.4% were HIV positive at baseline and 90% were followed at 6 months; 3 of 778 seroconverted, for an incidence of 0.87/100 person years. (Previous RTA cohorts have had an incidence of 3.4%/year). Among 380 men discharged from RTA, follow-up at 9 months was 81.8% and the incidence was 5.2/100 person years. Sample sizes required to show an HIV vaccine efficacy of 60%, with a power-.90, alpha-.05 varies from CSUs 644, STD patients 1456 to ex-RTA-1306. Several populations in northern Thailand appear to have sufficiently high HIV-1 incidence and adequate follow-up for HIV vaccine efficacy trials and other preventive intervention trials.


Occult pneumothorax in Chinese patients with significant blunt chest trauma: incidence and management.
Occult pneumothorax (OP) is a pneumothorax not visualised on a supine chest X-ray (CXR) but detected on computed tomography (CT) scanning. With increasing CT use for trauma, more OP may be detected. Management of OP remains controversial, especially for patients undergoing mechanical ventilation. This study aimed to identify the incidence of OP using thoracic CT as the gold standard and describe its management amongst Hong Kong Chinese trauma patients. Analysis of prospectively collected trauma registry data. Consecutive significantly injured trauma patients admitted through the emergency department (ED) suffering from blunt chest trauma who underwent thoracic computed tomography (TCT) between in calendar years 2007 and 2008 were included. An OP was defined as the identification (by a specialist radiologist) of a pneumothorax on TCT that had not been previously detected on supine CXR. 119 significantly injured patients were included. 56 patients had a pneumothorax on CXR and a further 36 patients had at least one OP [OP incidence 30% (36/119)]. Bilateral OP was present in 8/36 patients, so total OP numbers were 44. Tube thoracostomy was performed for 8/44 OP, all were mechanically ventilated in the ED. The remaining 36 OP were managed expectantly. No patients in the expectant group had pneumothorax progression, even though 8 patients required subsequent ventilation in the operating room for extrathoracic surgery. The incidence of OP (seen on TCT) in Chinese patients in Hong Kong after blunt chest trauma is higher than that typically reported in Caucasians. Most OP were managed expectantly without significant complications; no pneumothorax progressed even though some patients were mechanically ventilated.


Acute presentation of multi-cystic peritoneal mesothelioma.
Multi-cystic peritoneal mesothelioma (MCPM) is a rare intra-abdominal neoplasm that occurs most commonly in young females. The disease usually presents as an incidental finding or with sub-acute abdominal pain. The mainstay of treatment is complete excision; however, local recurrence frequently occurs and malignant transformation has been reported. We describe a unique case of MCPM that presented with acute abdominal pain. A 32-year-old female presented with a 24-hour history of abdominal pain. Computed tomography abdomen demonstrated a low-density mass with surrounding inflammatory changes anterior to the ascending colon, which was initially thought to represent an abscess. A percutaneous drain was inserted; however, only clear fluid was aspirated and the lesion did not resolve. The patient subsequently underwent laparoscopy which identified a cystic structure overlying the ascending colon. The structure was excised whole with histology demonstrating MCPM. The patient recovered from surgery and will undergo a period of surveillance.


MoRic8 Is a novel component of G-protein signaling during plant infection by the rice blast fungus Magnaporthe oryzae.
An insertional mutagenesis screen was used to investigate the biology of plant infection by the devastating rice blast pathogen, Magnaporthe oryzae. Here, we report the identification of a new mutant, LY-130, which is defective in multiple steps during infection-related morphogenesis and pathogenicity. Analysis of the mutation confirmed an insertion into gene MoRIC8, which encodes a 480-amino-acid protein that is a putative homologue of the Ric8 regulator of GTP-binding protein (G-protein) signaling, previously described in animals. Targeted gene deletion mutants of MoRIC8 were nonpathogenic and impaired in cellular differentiation associated with sporulation, sexual development, and plant infection. MoRic8 physically interacts with the Galpha subunit MagB in yeast two-hybrid assays and appears to act upstream of the cyclic AMP response pathway that is necessary for appressorium morphogenesis. Taken together, our results indicate that MoRic8 may act as a novel regulator of the G-protein signaling during infection-related development of rice blast fungus M. oryzae.


Concepts Describing and Assessing Individuals' Environmental Sustainability: An Integrative Review and Taxonomy.
The need to encourage individuals as active change agents for sustainability transitions has led researchers across disciplines to conceptualize over 70 constructs to assess relevant dispositions to environmental protection and green consumption behaviors. The generated knowledge is, however, fragmented by an unconsolidated set of constructs developed within parallel literature streams. We, hence, use an integrative review method to capture conceptual and operational similarities and distinctiveness of constructs across disciplines in the literature, attempting to unify the knowledge base. Thereby, we identify 34 conceptually distinct constructs (along with 38 synonyms and 76 scales) relevant for the thematic synthesis on individual-level constructs framing contributions to environmental measures and issues. We followingly propose a taxonomy, systemizing constructs based on their concept type(s) (e.g., value, attitude, behavior) and contextual scope(s) of the environmental challenge (e.g., product choice, household practice) addressed. We capture these dimensions in critically assessing relevant and salient conceptual and operational features. We thus create a consolidated picture of extant constructs capturing individual-level environmental sustainability by which we intend a three-fold contribution to the interdisciplinary field. First, the taxonomy and guiding framework for the choice of constructs should assist substantive researchers in identifying appropriate constructs of interest. Second, the systematic integration of (dis)similar concepts available in parallel literature streams should assist future endeavors aiming at integrating substantive findings with regard to antecedents, consequences, and other relevant variables. Finally, the taxonomy revealed that conceptualizations mainly scatter around specific combinations of types and scopes while others remain unaddressed. Based on our critical assessment of the relevant features and resulting taxonomy, we identify avenues for future research dedicated to (i) enhancing conceptual rigor and measurement quality in the field and (ii) introducing concepts addressing missing but potentially valuable combinations of types and scopes (e.g., antecedents capturing green consumption contexts). We conclude that researchers engaging in the proposed avenues with conceptual, methodological, or empirical contributions should consider four critical aspects to advance knowledge accumulation and prevent fragmentation in the interdisciplinary field. We thereby hope to pave the way for a collective, interdisciplinary knowledge base of concepts used to describe and assess individual's pro-environmental dispositions and practices of green consumption.


Surgical Outcomes of Cox-maze IV Procedure Using Bipolar Irrigated Radiofrequency Ablation and Cryothermy in Valvular Heart Disease.
We evaluated the efficacy of Cox-maze IV procedure using bipolar irrigated radiofrequency ablation and cryothermy in chronic atrial fibrillation associated with valvular heart disease. From November 2005 to June 2009, ninety four patients have undergone valvular heart surgery with Cox-maze IV procedure. Preoperative duration of atrial fibrillation was 7.6±6.5 years and follow-up duration was 22.7±12.3 months. There were two (2.1%) postoperative deaths not related to maze procedure. Two cerebrovascular accidents, five low cardiac output syndromes and two permanent pacemaker implantations have occurred after surgery. Preoperative ejection fraction on echocardiography was 55.3±8.1% and ejection fraction of postoperative six month was 54.7±6.5%. Left atrial size of preoperative and postoperative were 61.5±11.6 mm and 53.1±8.4 mm at each. Freedom from atrial fibrillation rate at postoperative six-month was 80.7% and the cases of recurrence of atrial fibrillation after six months were three (3.3%). Risk factors for failure or recurrence of maze procedure were old age (p=.010) and preoperative moderate or severe tricuspid regurgitation (p=.033). The Cox-maze IV procedure using RFBP2 and cryothermy is quite safe and freedom from atrial fibrillation at postoperative 6 month was 82.5%. Risk factors for failure or recurrence of atrial fibrillation after Cox-maze IV were old age and preoperative over moderate tricuspid regurgitation.


Review of five consecutive studies of radiolabeled immunoglobulin therapy in Hodgkin's disease.
Recurrent Hodgkin's Disease (HD) provides unique opportunities to improve radiolabeled immunoglobulin therapy (RIT). Normal tissue toxicity after RIT is limited to bone marrow damage and is well documented and quantified in HD patients. Anti-antibody formation is rare in patients with HD, allowing for multiple RIT cycles. Overall, 134 patients with recurrent HD were treated on five different studies with i.v. antiferritin, labeled with 131I or with 111In for diagnostic purposes and 90Y for therapeutic purposes. Patients with recurrent, end-stage HD obtain a 60% response rate following 90Y-labeled antiferritin. One-half of the therapy responses are complete. Responses are more common in patients with longer disease histories (> 3 years) and smaller tumor volumes (< 30 cm3) and in patients receiving at least 0.4 mCi 90Y-labeled antiferritin/kg body weight. Complete responders survive significantly longer than partial responders (2 years versus 1 year). Partial responders survive longer than patients with progressive disease (1 year versus 4 months). HD in one-third of the patients recurs in new areas. A low protein dose (2-5 mg) and a moderate specific activity (10 mCi/mg) are recommended. Results obtained with 90Y-labeled antiferritin are significantly better than results with 131I-labeled antiferritin. Further translational research in vitro in the radio pharmacy and in vivo with experimental animals is ongoing to improve the therapeutic results of RIT in HD. Obviously, many permutations of RIT cannot be explored in HD patients for ethical, financial, or logistic reasons, and predictive preclinical research is required to achieve further progress. Currently, RIT is a low-toxicity, low-cost outpatient procedure for recurrent HD with a high response rate in a patient population with an unfavorable prognosis.


Washington state foster care: dental utilization and expenditures.
To identify factors associated with dental utilization and expenditures for children enrolled in Washington State (WA) foster care (FC). This cross-sectional study used 2008 Medicaid enrollment and claims files for children ages <18 years enrolled in the WA FC program for ≥11 months (N = 10,177). Regression models were used to examine associations between utilization and expenditures and sex, race, age group, Supplemental Security Income (SSI) (i.e., disability), substance abuse, behavior problems, placement setting (Foster Home Care, Kinship Care, Group Care, Other), and urbanicity. Only 43 percent of the children utilized any dental care; the adjusted mean expenditure was $198.35 [95% confidence interval (CI) $181.35, $215.36]. Fewer utilized diagnostic (41 percent), preventive (39 percent), restorative (11 percent), or complex (5 percent) services. Associated with utilization (P ≤ 0.01) were: female [ARR = 1.05, 95% CI(1.01, 1.10)]; 0-2 years [ARR = 0.18, 95% CI(0.15, 0.21)], [3-5 years ARR = 0.78, 95% CI(0.74, 0.83)]; Native American [ARR = 0.85, 95% CI(0.80, 0.91)]; SSI [ARR = 1.10, 95% CI(1.04, 1.17)]; Kinship Care [ARR = 0.94, 95% CI(0.90, 0.98)]; Group Care [ARR = 1.25 95% CI(1.15, 1.37)]; and urban/rural urbanicity with population <20 K [ARR = 1.20 95% CI(1.12, 1.30)]. Associated with expenditures (P < 0.05) were: ages 0-2 years [-$153.66, 95% CI(-$168.33, -$139.00)], 3-5 years [-$98.71, 95% CI(-$116.78, -$80.65)], 6-11 years [-$16.83 95% CI(-$33.52, -$0.14)]; African American [-$32.05 95% CI(-$47.99, -$16.12)]; Kinship Care [$28.57 95% CI($14.00, $43.15)]. Most children enrolled in WA FC for ≥11 months during 2008 did not receive dental care. Research is needed to determine the level of unmet need among children in FC and interventions to improve access to oral health of the children. Enforcement of existing federal legislation is needed.


National guidelines for the management of HIV-1 in pregnancy.
Management of HIV-1 in pregnancy has reduced the mother-to-child-transmission (MTCT) rate from 25-30% to <2% in the developed world, including Ireland. In Ireland most HIV positive pregnant women are diagnosed through antenatal screening many of whom arrive here late in pregnancy. Geographic dispersal and subsequent involvement of obstetric units throughout the country has resulted in a need for clear, accessible management guidelines. The Irish Infection Society first published guidelines for the management of HIV-1 in pregnancy in 2001 (1). The updated guidelines became operational in January 2002 with some amendments in March 2003 and July 2004. These guidelines offer a broad management outline for HIV positive pregnant women. Ultimately, each woman is assessed individually by a multidisciplinary team and a careful plan is determined.


Solution-based synthesis and design of late transition metal chalcogenide materials for oxygen reduction reaction (ORR).
Late transition metal chalcogenide (LTMC) nanomaterials have been introduced as a promising Pt-free oxygen reduction reaction (ORR) electrocatalysts because of their low cost, good ORR activity, high methanol tolerance, and facile synthesis. Herein, an overview on the design and synthesis of LTMC nanomaterials by solution-based strategies is presented along with their ORR performances. Current solution-based synthetic approaches towards LTMC nanomaterials include a hydrothermal/solvothermal approach, single-source precursor approach, hot-injection approach, template-directed soft synthesis, and Kirkendall-effect-induced soft synthesis. Although the ORR activity and stability of LTMC nanomaterials are still far from what is needed for practical fuel-cell applications, much enhanced electrocatalytic performance can be expected. Recent advances have emphasized that decorating the surface of the LTMC nanostructures with other functional nanoparticles can lead to much better ORR catalytic activity. It is believed that new synthesis approaches to LTMCs, modification techniques of LTMCs, and LTMCs with desirable morphology, size, composition, and structures are expected to be developed in the future to satisfy the requirements of commercial fuel cells.


Cationic lipid binding to DNA: characterization of complex formation.
We recently demonstrated that cationic lipids, added in monomer or micellar form, bind to DNA, resulting in the formation of a hydrophobic complex. This complex can serve as a well-defined intermediate in the preparation of DNA-lipid particles (DLPs) with many potential applications for delivery of polynucleotides in vitro and in vivo. To develop a better understanding of the factors governing complex formation, we have characterized the cationic lipid/DNA binding reaction. This was evaluated by measuring DNA and cationic lipid (DODAC) complex formation using the Bligh and Dyer extraction procedure. Efficient recovery of DNA (> 95%) in the organic phase was achieved when sufficient monocationic lipids interact with DNA phosphate groups. The rate of binding depends on the amount of DNA or cationic lipid present in the system. The time required to generate the hydrophobic complex was increased when < 10 micrograms of DNA or < 40 nmol of DODAC was present. Surprisingly, the rate of complex formation was contingent on the incubation period after partitioning the DNA/lipid mixture into organic and aqueous phases. These results suggest that the cationic lipid/DNA complex forms at the aqueous/organic interface and that DNA/lipid binding is dependent on multivalent interactions at this interface. A Scatchard analysis of DNA/DODAC binding demonstrated that the binding reaction exhibits a high degree of positive cooperativity. The apparent dissociation constant (Kn), using data obtained under conditions where DODAC binding to DNA approached saturation, indicated a high-affinity reaction (Kn > 10(-11) mol L-1). At this point, approximately 8400 mol of DODAC was bound per mole of DNA, which is equivalent to a charge ratio (+/-) of 0.585 for the 7.2 kb plasmid used and suggests that formation of the hydrophobic complex occurs at a stage prior to charge neutralization. The influence of other lipids on DNA/cationic lipid binding at the aqueous/organic interface was also studied. Cholesterol and DOPC had little effect on DNA/DODAC binding while the anionic lipids LPI, DOPS, and DMPG inhibited complex formation. The zwitterionic lipid DOPE, however, had a concentration-dependent effect on cationic lipid binding that was also dependent on the mixing order. We believe that this approach for evaluating lipid/DNA binding provides an effective procedure for assessing factors which control the dissociation of lipids from DNA and may be beneficial in the selection of lipids for effective use in gene transfection studies.


Automated Manipulation of Miniature Objects Underwater Using Air Capillary Bridges: Pick-and-Place, Surface Cleaning, and Underwater Origami.
Various insects can entrap and stabilize air plastrons and bubbles underwater. When these bubbles interact with surfaces underwater, they create air capillary bridges that de-wet surfaces and even allow underwater reversible adhesion. In this study, a robotic arm with interchangeable three-dimensional (3D)-printed bubble-stabilizing units is used to create air capillary bridges underwater for manipulation of small objects. Particles of various sizes and shapes, thin sheets and substrates of diverse surface tensions, from hydrophilic to superhydrophobic, can be lifted, transported, placed, and oriented using one- or two-dimensional arrays of bubbles. Underwater adhesion, derived from the air capillary bridges, is quantified depending on the number, arrangement, and size of bubbles and the contact angle of the counter surface. This includes a variety of commercially available materials and chemically modified surfaces. Overall, it is possible to manipulate millimeter- to sub-millimeter-scale objects underwater. This includes cleaning submerged surfaces from colloids and arbitrary contaminations, folding thin sheets to create three-dimensional structures, and precisely placing and aligning objects of various geometries. The robotic underwater manipulator can be used for automation and control in cell culture experiments, lab-on-chip devices, and manipulation of objects underwater. It offers the ability to control the transport and release of small objects without the need for chemical adhesives, suction-based adhesion, anchoring devices, or grabbers.


Pattern size reduction effect via a "mix and match" sequential imprinting technique.
Nanoimprint lithography is traditionally thought of as a one-to-one pattern replication process, where the negative of the surface relief pattern from a mold is reproduced exactly onto a resist material. As such, each pattern design will require a mold to be fabricated with the pattern required. The mold used is typically fabricated by various lithographic processes, many of which are costly and time-consuming. In this work, we report the use of a "mix and match" sequential imprinting technique where line-space patterns of different gap sizes were achieved through the different combinations of feature size and relative alignments of the molds. More significantly, patterns with gap sizes smaller than the molds were obtained, resulting in a size reduction effect. A gap size reduction as high as 93% had been achieved in imprinted polystyrene and we have exploited the patterns as shadow masks used for the deposition of nanometer sized metal lines. The main advantage of this gap size reduction effect lies in the tunability of the process, which removes the need for the design and purchase of newer and more expensive imprinting molds.


Rapid village survey to determine the size of the leprosy problem in Khon Kaen Province, Thailand.
The rapid village survey (RVS) method has been developed as a simpler, less-expensive alternative to random sample surveys for determining the prevalence of leprosy and was compared with a total population survey (TVS). In the RVS, the cluster population receives clear information about the disease, and those with symptoms are invited to be examined by the survey team. A list of household contacts and suspects was made and those on the list were actively traced. The registered population was 20,815; 10 new patients were found among the 2034 people self-reporting in the RVS, 0 among the household contacts and suspects, and an additional 2 new patients in the TVS. There were 12 registered patients among the sample population. The prevalence rate found by the RVS was 1.06 per 1000(95% CI = 0.49-1.63) and in the TVS 1.16 per 1000 (95% CI = 0.5-1.77). The man-days and costs of an RVS are considerably less than those for a TVS. It was concluded that the RVS is a valid replacement for the TVS as conducted in Khon Kaen Province, Thailand. The RVS can be applied under low-endemic conditions and could be carried out by the general health staff.


Cell wall substrate specificity of six different lysozymes and lysozyme inhibitory activity of bacterial extracts.
We have investigated the specificity of six different lysozymes for peptidoglycan substrates obtained by extraction of a number of gram-negative bacteria and Micrococcus lysodeikticus with chloroform/Tris-HCl buffer (chloroform/buffer). The lysozymes included two that are commercially available (hen egg white lysozyme or HEWL, and mutanolysin from Streptomyces globisporus or M1L), and four that were chromatographically purified (bacteriophage lambda lysozyme or LaL, bacteriophage T4 lysozyme or T4L, goose egg white lysozyme or GEWL, and cauliflower lysozyme or CFL). HEWL was much more effective on M. lysodeikticus than on any of the gram-negative cell walls, while the opposite was found for LaL. Also the gram-negative cell walls showed remarkable differences in susceptibility to the different lysozymes, even for closely related species like Escherichia coli and Salmonella Typhimurium. These differences could not be due to the presence of lysozyme inhibitors such as Ivy from E. coli in the cell wall substrates because we showed that chloroform extraction effectively removed this inhibitor. Interestingly, we found strong inhibitory activity to HEWL in the chloroform/buffer extracts of Salmonella Typhimurium, and to LaL in the extracts of Pseudomonas aeruginosa, suggesting that other lysozyme inhibitors than Ivy exist and are probably widespread in gram-negative bacteria.


The effects of various secretagogues on the mucin content of pure submandibular salivas.
The concentrations of a specific mucin and total protein were compared in pure submandibular saliva samples elicited by pilocarpine (PILO), epinephrine (EPI), and isoproterenol (IPR) in mice. At the dosages employed, IPR-stimulated samples contained, on the average, the highest concentrations of protein and mucin. EPI samples contained intermediate levels, and PILO the lowest concentrations. The average mucin-to-protein ratio in the PILO saliva samples was intermediate between the IPR and EPI samples. Non-stimulated saliva samples showed a broader range of mucin to total protein than did the stimulated saliva sets. Within the PILO saliva samples, there was a very strong positive correlation between the mucin content of saliva and the mucin content in the pre-secretory gland prior to stimulation. The mucin content of EPI and IPR samples also showed strong positive relationships with the content of mucin in the gland. The mucin and protein in EPI saliva samples were significantly correlated in at least one of the collections, whereas in the IPR samples, there was a much weaker relationship. With the exception of the third sequential collection of EPI saliva, all nine of the other EPI, IPR, and PILO collection sets showed only a weakly negative or no correlation between flow rate and saliva mucin or protein content. This is in sharp contrast with the strongly negative correlation which was noted between saliva protein or mucin contents and flow rate when all of the data were combined. These observations suggest that the nature of the stimulant is a very important determinant of overall flow rates, saliva protein, and mucin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of acute Chlamydia pneumoniae infection on lipoprotein metabolism in NIH/S mice.
Chlamydia pneumoniae is a well-known cause of respiratory infections, globally. Chronic C. pneumoniae infection has been associated with atherosclerosis. The aim of the present study was to investigate the effects of acute C. pneumoniae infection on serum lipid levels and some regulatory proteins/enzymes in NIH/S mice. Female mice (n=30) were intranasally infected with 5.3*10(5) inclusion forming units (IFU) of C. pneumoniae and control mice (n = 30) were inoculated with buffer. Six uninoculated mice at day 0 and then six mice from each group 3, 6, 9, 14 and 20 days post-inoculation were killed and serum samples were collected for analysis. Successful infection was confirmed by IgG response to C. pneumoniae and positive Chlamydia cultivation from the lungs. Serum triglycerides and total cholesterol, as well as the activities of hepatic lipase (HL), lecithin-cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) and the concentration of lipopolysaccharide-binding protein (LBP) were analyzed. In C. pneumoniae infected mice, a minor change in triglyceride (corrected p-value 0.020) levels was observed 9 days post-infection (p.i.). LCAT activity declined remarkably, and the lowest activities were measured on day 9 p.i. (67% from the baseline value). HL and PLTP activities did not differ from those in the control group during the whole experimental period. There was a 2.5-fold increase in the serum LBP concentration owing to the C. pneumoniae infection 9 days p.i. The data indicate that acute C. pneumoniae infection, although clinically almost asymptomatic, causes small, transient changes in serum total lipids and some key proteins involved in lipoprotein metabolism in mice.


Oxygen-15 labeled CO2, O2, and CO PET in small animals: evaluation using a 3D-mode microPET scanner and impact of reconstruction algorithms.
Positron emission tomography (PET) studies using 15O-labeled CO2, O2, and CO have been used in humans to evaluate cerebral blood flow (CBF), the cerebral oxygen extraction fraction (OEF), and the cerebral metabolic rate of oxygen (CMRO2) and cerebral blood volume (CBV), respectively. In preclinical studies, however, PET studies using 15O-labeled gases are not widely performed because of the technical difficulties associated with handling labeled gases with a short half-life. The aims of the present study were to evaluate the scatter fraction using 3D-mode micro-PET for 15O-labeled gas studies and the influence of reconstruction algorithms on quantitative values. Nine male SD rats were studied using the steady state inhalation method for 15O-labeled gases with arterial blood sampling. The resulting PET images were reconstructed using filtered back projection (FBP), ordered-subset expectation maximization (OSEM) 2D, or OSEM 3D followed by maximum a posteriori (OSEM3D-MAP). The quantitative values for each brain region and each reconstruction method were calculated by applying different reconstruction methods. The quantitative values for the whole brain as calculated using FBP were 46.6 ± 12.5 mL/100 mL/min (CBF), 63.7 ± 7.2% (OEF), 5.72 ± 0.34 mL/100 mL/min (CMRO2), and 5.66 ± 0.34 mL/100 mL (CBV), respectively. The CBF and CMRO2 values were significantly higher when the OSEM2D and OSEM3D-MAP reconstruction methods were used, compared with FBP, whereas the OEF values were significantly lower when reconstructed using OSEM3D-MAP. We evaluated the difference in quantitative values among the reconstruction algorithms using 3D-mode micro-PET. The iterative reconstruction method resulted in significantly higher quantitative values for CBF and CMRO2, compared with the values calculated using the FBP reconstruction method.


The assessment and treatment of behavioural problems.
While general practitioners acknowledge their responsibility for the medical management of people with intellectual disability and autism, there may be a need for more skill in the assessment and management of behavioral problems. This article provides an overview of services for this group of patients, the role of the GP, and provides a guide to assessment and treatment of behavioural problems. While GPs have skills in medical and psychiatric assessment, the different social, cognitive and communicative context in this group of people limits their ability to apply those skills. Nonetheless, familiarity with the patient and their social environment means that GPs have an important and central role in the ongoing management of patients with an intellectual disability.


Digalactosyldiacylglycerol Synthase Gene MtDGD1 Plays an Essential Role in Nodule Development and Nitrogen Fixation.
Little is known about the genes participating in digalactosyldiacylglycerol (DGDG) synthesis during nodule symbiosis. Here, we identified full-length MtDGD1, a synthase of DGDG, and characterized its effect on symbiotic nitrogen fixation in Medicago truncatula. Immunofluorescence and immunoelectron microscopy showed that MtDGD1 was located on the symbiosome membranes in the infected cells. β-Glucuronidase histochemical staining revealed that MtDGD1 was highly expressed in the infection zone of young nodules as well as in the whole mature nodules. Compared with the control, MtDGD1-RNA interference transgenic plants exhibited significant decreases in nodule number, symbiotic nitrogen fixation activity, and DGDG abundance in the nodules, as well as abnormal nodule and symbiosome development. Overexpression of MtDGD1 resulted in enhancement of nodule number and nitrogen fixation activity. In response to phosphorus starvation, the MtDGD1 expression level was substantially upregulated and the abundance of nonphospholipid DGDG was significantly increased in the roots and nodules, accompanied by corresponding decreases in the abundance of phospholipids such as phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol. Overall, our results indicate that DGD1 contributes to effective nodule organogenesis and nitrogen fixation by affecting the synthesis and content of DGDG during symbiosis.


Voriconazole -- better chances for patients with invasive mycoses.
The past two decades have witnessed an increase in serious fungal infections, without corresponding growth in available antifungal agents. Voriconazole (VRC) is a novel triazole antifungal, recently approved in Europe for treatment of serious infections caused by Aspergillus, Fusarium, Scedosporium, and resistant Candida species. Voriconazole has in vitro activity against yeasts and yeast-like fungi similar, or superior to, fluconazole (FLC), itraconazole (ITC) and amphotericin B (AMB). Candida albicans is generally the most susceptible yeast (VRC MIC subset90 of 0.06 microg/ml); C. krusei often has low MICs even in the face of FLU/ITC resistance. Voriconazole has demonstrated comparable, or better, in vitro activity than ITC and AMB against Aspergillus (mean MICs 0.19-0.58 microg/ml), Ascomycetes, Bipolaris, Fusarium, Blastomyces dermatitidis, Coccidioides immitis, dermatophytes, Histoplasma capsulatum, Malassezia, and Scedosporium angiospermum (P. boydii). The drug possesses potent fungicidal activity against moulds including Aspergillus, Scedosporium, and Fusarium. Fungicidal activity is likely due to the high affinity of VRC for fungal 14-alpha-demethylase, a concept supported by ultrastructural and biochemical analysis. Animal studies confirmed the activity of VRC against infections including pulmonary and invasive aspergillosis (IA); A. fumigatus endocarditis; fusariosis; pulmonary cryptococcosis; and invasive candidiasis. Most importantly, well-designed human clinical trials have confirmed the efficacy of VRC in the treatment of candidal esophagitis, IA, and febrile neutropenia. Smaller studies and case reports have shown VRC is useful for salvage therapy of IA, cerebral aspergillosis, Scedosporium, and other fungal infections. Clinical testing has shown VRC is safe and well tolerated; the most common side effect is benign, self-limited visual disturbance.


[Mystery of Yiyin decoction theory: rule discovery and evaluation strategy of atypical pharmacological effects of Chinese medicinal prescription].
Yi Yin, a famous medical scientist and culinary master in the late Xia Dynasty and early Shang Dynasty, developed the Chinese medicinal liquids and Chinese medicinal prescriptions emerged after that. Chinese medicinal prescriptions have attracted much attention because of their unique advantages in the treatment of chronic multifactorial diseases, representing an important direction of drug discovery in the future. Yiyin decoction theory is the superior form of personalized combined medication with advanced consciousness. It is different from not only the magic bullet theory of single component action but also the connotation of modern multi-target drugs. The core of Yiyin decoction theory can be summarized as compound compatibility, multiple effects, and moderate regulation. Compound compatibility refers to that the formulation of Chinese medicinal prescriptions involves the complex synergy and interactions between sovereign, minister, assistant, and guide medicinal materials. Multiple effects mean that the prescriptions employ a variety of mechanisms to exert comprehensive pharmacological effects of nonlinear feedback. Moderate regulation reflects that the prescriptions can accurately regulate the multiple points of the disease biological network as a whole. To solve the mystery of Yiyin decoction theory, we should not only simply study the known active substances(components) and their independent target effects in the mixture, but also mine the "dark matter" and "dark effect" of Chinese medicinal prescriptions. That is, we should learn the neglected atypical pharmacological effects of Chinese medicinal prescriptions and the multi-point nesting mechanism that plays a precise regulatory function in the body. Yiyin decoction theory focuses on the overall pharmacological effect to reflect the comprehensive clinical value of Chinese medicinal prescriptions, which is of great significance for the development of a new model for the evaluation and application of new Chinese medicinal prescriptions in line with the theory of traditional Chinese medicine.


Externally imposed electric field enhances plant root tip regeneration.
In plants, shoot and root regeneration can be induced in the distinctive conditions of tissue culture (in vitro) but is also observed in intact individuals (in planta) recovering from tissue damage. Roots, for example, can regenerate their fully excised meristems in planta, even in mutants with impaired apical stem cell niches. Unfortunately, to date a comprehensive understanding of regeneration in plants is still missing. Here, we provide evidence that an imposed electric field can perturb apical root regeneration in Arabidopsis. Crucially, we explored both spatial and temporal competences of the stump to respond to electrical stimulation, by varying respectively the position of the cut and the time interval between excision and stimulation. Our data indicate that a brief pulse of an electric field parallel to the root is sufficient to increase by up to two-fold the probability of its regeneration, and to perturb the local distribution of the hormone auxin, as well as cell division regulation. Remarkably, the orientation of the root towards the anode or the cathode is shown to play a role.